Dissolved organic matter quantity and quality response of tropical rainforest headwater rivers to the transition from dry to wet season.

Dissolved organic matter (DOM) and its composition in aquatic ecosystems is a key indicator of ecosystem function and an important component of the global carbon cycle. Tropical rainforest headwaters play an important role in global carbon cycling. However, there is a large uncertainty on how DOM sources interact during mobilisation and the potential fate of associated carbon and nutrients. Using field techniques to measure dissolved organic carbon (DOC) concentration and composition, changes in DOM source from headwaters to larger downstream rivers were observed. This study shows that the hydrological connectivity, developed during the transition from dry to wet seasons, changes the DOM supply and transport across a tropical river catchment. The observed variability in the DOC-river discharge relationship provides further evidence of the changes in the DOM supply in a small headwater. This novel insight into the seasonal changes of the dynamics of DOM supply to the river helps understanding the mobilization of terrestrial DOM to tropical headwaters and its export from smaller to larger rivers. It also highlights the data gap in the study of smaller headwaters which may account for uncertainty in estimating the terrestrial carbon transported by inland waters.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/µL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

Estimability and dependency analysis of model parameters based on delay coordinates.

In data-driven system identification, values of parameters and not observed variables of a given model of a dynamical system are estimated from measured time series. We address the question of estimability and redundancy of parameters and variables, that is, whether unique results can be expected for the estimates or whether, for example, different combinations of parameter values would provide the same measured output. This question is answered by analyzing the null space of the linearized delay coordinates map. Examples with zero-dimensional, one-dimensional, and two-dimensional null spaces are presented employing the Hindmarsh-Rose model, the Colpitts oscillator, and the Rössler system.

The role of peripheral afferents in persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial of ultrasound-guided tender point blockade.

BACKGROUND: Severe, persistent inguinal postherniorrhaphy pain (PIPP) is a debilitating condition that develops in 2-5% of patients. PIPP may be neuropathic in nature, yet the lesion in the peripheral nervous system has not been located. Most PIPP-patients demonstrate a tender point (TP) in the medial aspect of the inguinal region that triggers pain upon minimal pressure. As TPs may play a role in the pathophysiology of PIPP, the aim of this trial was to investigate the analgesic effects of local anaesthetic TP-blockade. METHODS: A randomized, double-blind, placebo-controlled, crossover trial was performed in 14 PIPP-patients and six healthy volunteers. All participated in two sessions, seven days apart, receiving 10 ml of 0.25% bupivacaine or normal saline via an ultrasound-guided fascial plane block at the TP. The TP-area was used for pain assessments (at rest, on movement, with 100 kPa pressure-algometry) and quantitative sensory testing (pressure pain thresholds, thermal detection/pain thresholds, supra-threshold heat perception), before and after the TP-blockade. RESULTS: The median (95% CI) reduction in pain was 63% (44.1 to 73.6%) after bupivacaine compared with 36% (11.6 to 49.7%; P=0.003) after placebo. Significant increases in cool detection (P=0.01) and pressure pain thresholds (P=0.009) with decreases in supra-threshold heat pain perception (P=0.003) were seen after bupivacaine only. In four out of six volunteers, increased thermal and evoked-pain thresholds after bupivacaine compared with placebo, was demonstrated. CONCLUSIONS: This trial demonstrates that peripheral afferent input from the TP-area is important for maintenance of spontaneous and evoked pain in PIPP. CLINICAL TRIAL REGISTRATION: NCT02065219.

Neandertal roots: Cranial and chronological evidence from Sima de los Huesos.

Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.

Propranolol targets the contractility of infantile haemangioma-derived pericytes.

BACKGROUND: Propranolol, a ß-adrenergic receptor (AR) antagonist, is an effective treatment for endangering infantile haemangioma (IH). Dramatic fading of cutaneous colour is often seen a short time after initiating propranolol therapy, with accelerated regression of IH blood vessels discerned after weeks to months. OBJECTIVES: To assess a possible role for haemangioma-derived pericytes (HemPericytes) isolated from proliferating and involuting phase tumours in apparent propranolol-induced vasoconstriction. METHODS: HemPericytes were assayed for contractility on a deformable silicone substrate: propranolol (10 µmol L(-1)) restored basal contractile levels in HemPericytes that were relaxed with the AR agonist epinephrine. Small interfering RNA knockdown of ß2-AR blunted this response. HemPericytes and haemangioma-derived endothelial cells were co-implanted subcutaneously in nude mice to form blood vessels; at day 7 after injection, mice were randomized into vehicle and propranolol-treated groups. RESULTS: HemPericytes expressed high levels of ß2-AR mRNA compared with positive control bladder smooth muscle cells. In addition, ß2-AR mRNA levels were relatively high in IH specimens (n = 15) compared with ß1-AR, ß3-AR and α1b-AR. Normal human retinal and placental pericytes were not affected by epinephrine or propranolol in this assay. Propranolol (10 µmol L(-1)) inhibited the proliferation of HemPericytes in vitro, as well as normal pericytes, indicating a nonselective effect in this assay. Contrast-enhanced microultrasonography of the implants after 7 days of treatment showed significantly decreased vascular volume in propranolol-treated animals, but no reduction in vehicle-treated animals. CONCLUSIONS: These findings suggest that the mechanism of propranolol's effect on proliferating IH involves increased pericytic contractility.

First Detection of Puccinia ballotiflora on Salvia greggii.

Salvia greggii, autumn sage, is grown for its bright red to white flowers that bloom in late summer and fall. In February of 2008, a rust sample was sent to the CDFA plant pathology diagnostics laboratory in Sacramento from a nursery in Santa Barbara County, CA. Pustules were abundant on older leaves causing moderate defoliation of containerized stock. Only the varieties with entirely red or pink flowers were affected. S. greggii 'Hotlips,' a popular white/red bicolor, was unaffected. Amphigenous uredinia were cinnamon brown, round, powdery, and sometimes surrounded by yellow halos. Pustules were found primarily on the leaves, although a few were on the stems. Urediniospores were broadly obovoid, subglobose to broadly ellipsoid, echinulate, and 22 to 27 × 24 to 32 µm (24.9 × 26.9 µm average) with one apical pore and 2 to 3 equatorial pores. Urediniospore walls were cinnamon brown in color and measured 1.0 to 2.0 µm (1.5 µm average). No telia were observed. After the initial detection, this rust was found in additional nursery sites in Santa Cruz, Santa Clara, Santa Barbara, and Ventura counties in 2008 and 2009. In November of 2011, a sample from a landscape planting in Santa Barbara County of a similar rust with telia and teliospores was submitted. Urediniospores and teliospores were present in the same lesions. Lesions with teliospores were located primarily on the stems. Mature teliospores were two-celled, verrucose, chocolate brown, and 25 to 31 × 32 to 40 µm (28.6 × 35.3 µm average) with a pedicel ranging from 8 to 12 × 38 to 104 µm, sometimes attached obliquely. The rust matched the morphological characteristics of Puccinia ballotiflora (Syn = P. ballotaeflora Long) (2). To confirm pathogenicity, three 20-cm-tall plants of S. greggii 'Navajo Red' in 3.8-liter pots were spray inoculated with 10 ml of a 2.5 × 103 urediniospores per ml suspension and incubated in a dew chamber at 23°C for 2 days in the dark. Plants were transferred to a growth chamber maintained at 22°C with a 12-h photoperiod. Three plants were sprayed with sterile distilled water as controls. Uredinial pustules (1 to 2 mm) appeared on the abaxial surface of the leaves after 3 weeks. The pathogenicity test was repeated with similar results. The internal transcribed spacer region of rDNA and a portion of the 28S rDNA were amplified with primer pairs ITS5 (5'-GGAAGTAAAAGTCGTAACAAGG-3'), Rust1 (5'-GCTTACTGCCTTCCTCAATC-3'), and Rust2inv (5'-GATGAAGAACACAGTGAAA-3'), LR6 (5'-CGCAGTTCTGCTTACC-3') as described by Aime (1) and sequenced using the amplification primers, Rust2 (5'-TTTCACTGTGTTCTTCATC-3') and Rust3 (5'-GAATCTTTGAACGCACCTTG-3'). BLAST query of the assembled sequence, GenBank KF381491, was 91% identical to P. acroptili, JN204194, its closest match of similar length. P. ballotiflora has been found in Colombia on S. cataractarum, S. petiolaris, and S. mayori (3), and in Texas and Mexico on S. ballotiflora (4). To the best of our knowledge, this is the first detection of P. ballotiflora on S. greggii worldwide. P. ballotiflora is already widespread in the nursery trade in California and frequent fungicide applications are necessary to keep plants marketable. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) J. W. Baxter and G. B. Cummins. Lloydia 14:201, 1951. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Botany and Mycology Laboratory, Online publication http://nt.ars-grin.gov/fungaldatabases ARS, USDA, 2014 (4) F. D. Kern et al. Mycologia 25:448, 1933.

First Published Report of Rust on White Alder Caused by Melampsoridium hiratsukanum in the United States.

White alder (Alnus rhombifolia) is a fast-growing tree native to the western United States and is planted frequently in landscapes. In September 2010, mature leaves of white alder with small, orange-yellow pustules were collected in a commercial nursery in Santa Cruz County, CA. Approximately 25 white alder trees were affected. Collected leaves were sent to the California Department of Food and Agriculture Plant Pest Diagnostics Laboratory. Young uredinial pustules were bullate, with urediniospores emerging from a single pore in the pustule. Spiny cells lined the ostiole. With age, pustules broke open to release more spores. Urediniospores were obovate to oval and measured from 14 to 20 × 27 to 41 µm (17.1 × 32.2 µm average, n = 62). Spores were uniformly echinulate and contained a nearly hyaline cell wall measuring from 1 to 2 µm (1.5 µm average) in thickness. A portion of the 28S ribosomal subunit (GenBank Accession No. KC313888) and the internal transcribed spacer regions (KC313889) were amplified and sequenced from DNA extracted from urediniospores using primers LR6 and rust2inv (1) and ITS1-F and ITS4-B (2), respectively. Our ITS sequence had 99% identity to GenBank accession EF564164, Melampsoridium hiratsukanum. In September 2011, white alder leaves with similar symptoms were collected from a commercial nursery in Santa Barbara County, CA. The spore morphology matched the white alder sample previously collected in Santa Cruz County, CA, in 2010. At that time, pathogenicity assays were conducted on three 1-year-old, 61-cm white alder trees planted in 3.8-liter pots. Six detached leaves with visible rust pustules were rubbed gently onto both the apical and distal side of moistened leaves of the healthy alders. Each infected leaf was used to inoculate a total of 6 to 10 healthy leaves by rubbing two leaves per tree before moving to the next tree. Leaves on three additional white alder trees were rubbed with healthy leaves as controls. Trees were incubated in a dew chamber for 3 days in darkness at 24°C, then placed in a growth chamber at 22°C with a 12-h photoperiod. Twelve days after inoculation, small lesions were visible on a few of the leaf undersides of each inoculated tree. Not all inoculated leaves developed pustules. No lesions developed on the control trees. M. hiratsukanum has been reported in Canada, Europe, and eastern Asia (3). There are no published reports of this rust in the United States, but there is an unpublished specimen from white alder in the USDA Systematic Mycology Herbarium (BPI 028048) collected from California in 1931, which was identified as M. hiratsukanum by G. B. Cummins using morphological criteria. We are unaware if older specimens of this rust exist because we were unable to search other herbaria in the United States. To the best of our knowledge, this rust has been present in California since 1931, but has only recently been found causing disease in nursery plants. There have been no reports of the serious foliar disease symptoms on trees in California wild lands as have been reported in Europe, presumably due to dry summer and fall seasons in white alder's natural habitat. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) M. Gardes and T. D. Bruns. Mol. Ecol. 2:113, 1993. (3) J. Hatula et al. Mycologia 101:622, 2009.

Influence of landmark and surgical variability on virtual assessment of total knee arthroplasty.

Given advances in recent years in imaging modalities and computational hardware/software, virtual analyses are increasingly valuable and practical for evaluating total knee arthroplasty (TKA). However, the influence of variabilities at each step in computational analyses on predictions of TKA performance for a population has not yet been thoroughly investigated, nor the relationship between these variabilities and expected variations in surgical practice. Understanding these influences is nevertheless essential for ensuring the clinical relevance of theoretical predictions. Here, a morphological analysis of proximal tibial resections within TKA is proposed and investigated. The goals of this analysis are to quantify the influence of variability in landmark detection on resection parameters and to evaluate this sensitivity relative to expected clinical variability in TKA resections. Results here are directly applicable to population-level computational analyses of morphological and functional TKA performance.

BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC.

The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.

Test-retest studies in quantitative sensory testing: a critical review.

Quantitative sensory testing (QST) investigates the graded psychophysical response to controlled thermal, mechanical, electrical or chemical stimuli, allowing quantification of clinically relevant perception and pain thresholds. The methods are ubiquitously used in experimental and clinical pain research, and therefore, the need for uniform assessment procedures has been emphasised. However, varying consistency and transparency in the statistical methodology seem to occur in the QST literature. Sixteen publications, evaluating aspects of QST variability, from 2010 to 2012, were critically reviewed in detail. A considerable heterogeneity in the statistical evaluations of test-retest data was demonstrated. The authors, using a secondary analysis of published data for didactic purposes, propose and present minimal requirements for reporting of test-retest QST data.

Pathogenesis of infantile haemangioma.

Haemangioma is a vascular tumour of infancy that is well known for its rapid growth during the first weeks to months of a child's life, followed by a spontaneous but slow involution. During the proliferative phase, the vessels are disorganized and composed of immature endothelial cells. When the tumour involutes, the vessels mature and enlarge but are reduced in number. Fat, fibroblasts and connective tissue replace the vascular tissue, with few, large, feeding and draining vessels evident. Both angiogenesis and vasculogenesis have been proposed as mechanisms contributing to the neovascularization in haemangioma tumours. In recent years, several of the 'building blocks', the cells comprising the haemangioma, have been isolated. Among them are haemangioma progenitor/stem cells, endothelial cells and pericytes. This review focuses on these cell types, and the molecular pathways within these cells that have been implicated in driving the pathogenesis of infantile haemangioma.

Long-term follow-up after mesh removal and selective neurectomy for persistent inguinal postherniorrhaphy pain.

PURPOSE: Persistent inguinal pain, influencing daily activities, is seen in about 5 % of patients following inguinal herniorrhaphy. Surgical treatment of patients with persistent postherniorrhaphy pain has been associated with pain relief and improvement in functional status. However, the detailed long-term outcome effects remain to be clarified. The aim of this study was to determine the long-term effects of mesh removal and selective neurectomy in patients with persistent postherniorrhaphy pain after previous open repair. METHODS: The study consecutively included 54 inguinal postherniorrhaphy pain patients treated with mesh removal and aimed neurectomy. Patients completed questionnaires evaluating pain intensity with a numerical rating scale (NRS) and pain-related functional impairment preoperatively, and, 3, 6, 12, 24, and 36 months postoperatively. Endpoints were changes in pain intensity and functional ability when comparing preoperative and postoperative assessments. RESULTS: Pain intensities (average, maximum, and during activity) were significantly lower at all time points during follow-up compared to preoperative values (p < 0.01 for all) with a reduction in median (IQR) average pain intensity from 6.0 (5.0-7.0) preoperatively to 3.0 (1.0-5.5) at 36-month follow-up. There was no association between positive pain outcome and intraoperative nerve identification (p = 0.47). The number of patients who reported a long-term negative effect of the operation (≥ 25 % increase in average pain intensity at 36-month follow-up) was 1 of 8. The functional ability was improved at 3 months after the operation (p < 0.01), but the improvement was not statistically significant in the follow-up period. Preoperative signs of depression, anxiety, and catastrophizing had no influence on outcome. CONCLUSIONS: Mesh removal and attempted neurectomy may provide long-lasting analgesic effects in most patients and with a small proportion being worse, without relation to pain history and operative findings. Detailed multicenter collaboration is required to define preoperative diagnostics and the indication for mesh removal and neurectomy, the exact surgical procedure (type of neurectomy) and with detailed follow-up.

Chemotherapy for 70-Year-Old Women with Breast Cancer in Germany: A Survey by the German Breast Group.

Aim: Around half of all women in Germany with breast cancer are older than 65 and approximately one third of them is older than 70 years of age. In theory, the preferred therapeutic management of women with breast cancer aged 65 and above corresponds to that formulated for younger patients and complies with the S3 Guidelines and the therapy recommendations formulated by AGO. To study the current therapies used to treat women with breast cancer aged 70 and above in Germany, a survey of the clinics of the German Breast Group (GBG) was done. Method: An online survey was carried out with requests sent to 599 physicians registered as principal investigators in the database of the GBG. The 12-item questionnaire was used to investigate the systematic therapeutic management of 70-year-old patients in different settings. The indication for chemotherapy was taken as a given. Results: In a neoadjuvant setting, 62 % of physicians opted for anthracycline and taxane-based therapy as did 56.6 % of physicians in an adjuvant setting. One third of physicians preferred a taxane-based therapy with the anti-angiogenesis inhibitor bevacizumab as first-line therapy for primary metastatic cancer and after anthracycline-based therapy. Capecitabine (around 30 %) and navelbine (around 20 %) were proposed as second-line neoadjuvant and adjuvant therapies after prior anthracycline- and taxane-based therapy. Conclusion: The chemotherapy regimen prescribed for women with breast cancer aged 70 and above in Germany appears to be relatively standardised and corresponds to the recommendations given in the S3 Guidelines and by the AGO Breast Committee.

Calcium homeostasis influences radiological fracture healing in postmenopausal women.

INTRODUCTION: Recent studies suggest that calcium and 25-[OH]-cholecalciferol represent substantial co-factors in fracture healing. However, there still seems to be no sustainable consensus regarding the influence on fracture healing patterns. In this study, the influence of calcium and vitamin D levels on fracture callus formation was prospectively analysed using pQCT scan. METHODS: 94 postmenopausal females with distal radius fractures and consecutive surgery were included. Calcium, 25-[OH]-cholecalciferol, parathyroid hormone and bone-specific alkaline phosphatase levels were obtained prior surgical treatment and after 6 weeks. A pQCT scan was performed on both sites. Bone mineral density and fracture callus area were determined after detecting the outer border contour at a threshold of 280 mg/ccm. Patients received daily supplements of 1000 mg calcium and 880 IU 25-[OH]-cholecalciferol. RESULTS: Mean 25-[OH]-cholecalciferol level was 19.61 ± 21.87 ng/ml, mean parathyroid hormone level was 52.6 ± 58.9 ng/l and mean Ca level was 2.23 ± 0.35 mmol/l. After 6 weeks of supplementation a significant increase of calcium (p < 0.001) and 25-[OH]-cholecalciferol (p < 0.001), and a significant decrease of parathyroid hormone (p < 0.001) levels were observed. Sixth week follow-up fracture callus area correlated significantly with postoperative normal range calcium levels on the fractured site (p = 0.006). Bone mineral density correlated with age (p < 0.001), but not with calcium and 25-[OH]-cholecalciferol levels after 6 weeks. All fractures presented timely adequate callus formation. CONCLUSION: Calcium and parathyroid hormone serum levels influence fracture callus area interpreted as fracture callus formation patterns. Calcium levels within physiological range accounted for highest fracture callus area. Therefore, a balanced calcium homeostasis is required for appropriate callus formation.

Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab -- a translational project in the neoadjuvant GeparQuinto trial.

BACKGROUND: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear. METHODS: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points. RESULTS: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031). CONCLUSION: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.

Does nerve identification during open inguinal herniorrhaphy reduce the risk of nerve damage and persistent pain?

PURPOSE: Nerve identification during open inguinal hernia herniorrhaphy has been suggested as one of the factors that may reduce the risk of development of persistent postherniorrhaphy pain. In this prospective study, we evaluated whether intraoperative inguinal nerve identification influenced the risk of development of persistent postherniorrhaphy pain, sensory dysfunction in the groin and functional ability score after open hernia repair. METHODS: A total of 244 men with a primary inguinal hernia underwent open Lichtenstein repair in a high-volume hernia surgery centre, where information on inguinal nerve identification was registered during operation. Before the operation and 6 months postoperatively, functional pain-related impairment was assessed with Activities Assessment Scale and pain intensity scores with Numeric Rating Scale (NRS 0-10). Quantitative sensory testing in the groin was performed before operation and 6 months postoperatively, in order to investigate intraoperative inguinal nerve damage. RESULTS: The intraoperative nerve identification rates for the iliohypogastric, ilioinguinal and genitofemoral nerves were 94.7, 97.5 and 21.3 %, respectively. Thirty-nine patients (16.0 %) had substantial pain-related functional impairment at 6 months follow-up. There was no difference in risk of development of substantial pain-related functional impairment in patients with identification compared with non-identification of the iliohypogastric nerve (P = 1.0), the ilioinguinal nerve (P = 0.59), the genitofemoral nerve (P = 0.40) or all nerves (P = 0.52). There were no differences in regard to sensory loss in the groin area or in regard to improvement in functional outcome following surgery, between patients with and without nerve identification. CONCLUSIONS: Although intraoperative inguinal nerve identification should be aimed at, other factors may contribute to the risk of nerve damage and persistent pain after open groin hernia repair.

hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases.

We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions. It was correlated to the expression of hMLH1 protein, microsatellite instability (MSI) of ECs and to the well-known clinico-pathological variables of cancer. The hMLH1 promoter methylation was detected in 24 out of 64 (37.5 %) primary ECs but only in one out of 18 (5.6 %) metastatic lesions investigated. Promoter hMLH1 hypermethylation was found more often in early stage ECs and was associated with a decrease of hMLH1 protein expression immunohistochemically. An inverse relationship between hMLH1 expression and clinical stage of the disease was found (p = 0.048). Interestingly, there was a significant correlation between MSI and hMLH1 protein expression level (p = 0.042). MSI phenotype was found more often in EC metastases compared to the primary tumors (66.7 % vs 29.3 %; p = 0.039). However, neither hMLH1 promoter hypermethylation nor MSI was independent predictive factors for patient's outcome. Using an in vitro model we showed that hMLH1 methylation is reversible. These data showed that hMLH1 methylation with a consequent protein decrease occurred early during EC tumorigenesis and may cause a MSI phenotype, which occurs relatively late. MSI may be an important mechanism supporting further the tumor progression. These findings may have importance for the specific chemosensitization of the primary tumors/metastases and can improve our understanding of endometrial carcinogenesis in humans.

First Report of Powdery Mildew Caused by Podosphaera euphorbiae-hirtae on Euphorbia tithymaloides in California.

Euphorbia tithymaloides (Euphorbiaceae; known as 'Jacob's ladder,' 'Devil's Backbone') is a perennial, succulent spurge, grown primarily as a border plant in ornamental landscapes. In June 2011 and February 2012, the California Department of Food and Agriculture Plant Pest Diagnostics Lab, Sacramento, CA, received an unusual powdery mildew sample on greenhouse-grown E. tithymaloides from a Ventura County, CA nursery. Disease incidence at the nursery was 100%. White mycelial patches were present on the stems and on both sides of the leaves. Over time, heavily infected branches defoliated and brownish, roughened, scabby lesions developed on the stems. Hyphae were thin-walled, up to 8 µm wide and developed nipple-shaped appressoria. Ellipsoid-ovoid conidia measured 21.0 to 32.5 × 13 to 18 µm (avg. 26.4 × 13.9 µm, n = 20) and formed in chains. The rDNA internal transcribed spacer (ITS) region was amplified with primers PFITS-F and PF5.8-R (4). The 387-bp sequence (GenBank JX006103) was 99% similar (346/347 bp) to Podosphaera euphorbia-hirtae (AB040306) from Acalypha australis (Euphorbiaceae) (3). Based on ITS similarity and culture morphology, the fungus was identified as P. euphorbiae-hirtae U. Braun & Somani (1,3). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves from the nursery onto the youngest leaves of three plants each of E. tithymaloides cultivars 'Nano' and 'Variegated.' Leaves of an equal number of control plants were pressed with healthy leaves. Plants were incubated in a dew chamber for 48 h after which they were transferred to a 22°C growth chamber with a 12-h photoperiod. The experiment was repeated once. White powdery mildew colonies formed after 7 days on 'Variegated' and 13 days on 'Nano'. Conidia measured 27.5 to 35.0 × 11 to 15 µm (avg. 30.5 × 12.6 µm, n = 30) which was within the range of P. euphorbia-hirtae. No symptoms developed on the control plants. P. euphorbiae-hirtae has been reported in Asia and the UK on E. tithymaloides and in Asia on A. australis (2). An asexual Oidium stage on Euphorbiaceae in Asia, Africa, Australia, Florida, Puerto Rico, Cuba, and the U.S. Virgin Islands may correspond to P. euphorbiae-hirtae (2). To our knowledge, this is the first report of P. euphorbiae-hirtae in California. Following the 2011 and 2012 detections, all E. tithymaloides plants in the Ventura County, CA nursery were destroyed. A regulatory trace back survey found that the plants were shipped from a Florida supplier, which was also shown to have an outbreak of P. euphorbiae-hirtae. The original source of the Florida E. tithymaloides plants was a 2010 shipment from Costa Rica. The host range of P. euphorbiae-hirtae is restricted to three landscape species in the Euphorbiaceae. References: (1) U. Braun. Beih. Nova Hedwigia 89:143, 1987. (2) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/index.cfm May 1, 2012. (3) T. Hirata. et al. Can. J. Bot. 78:1521, 2000. (4) R. Singh et al. Plant Dis. 93:1348, 2009.

Asperisporium and Pantospora (Mycosphaerellaceae): epitypifications and phylogenetic placement.

The species-rich family Mycosphaerellaceae contains considerable morphological diversity and includes numerous anamorphic genera, many of which are economically important plant pathogens. Recent revisions and phylogenetic research have resulted in taxonomic instability. Ameliorating this problem requires phylogenetic placement of type species of key genera. We present an examination of the type species of the anamorphic Asperisporium and Pantospora. Cultures isolated from recent port interceptions were studied and described, and morphological studies were made of historical and new herbarium specimens. DNA sequence data from the ITS region and nLSU were generated from these type species, analysed phylogenetically, placed into an evolutionary context within Mycosphaerellaceae, and compared to existing phylogenies. Epitype specimens associated with living cultures and DNA sequence data are designated herein. Asperisporium caricae, the type of Asperisporium and cause of a leaf and fruit spot disease of papaya, is closely related to several species of Passalora including P. brachycarpa. The status of Asperisporium as a potential generic synonym of Passalora remains unclear. The monotypic genus Pantospora, typified by the synnematous Pantospora guazumae, is not included in Pseudocercospora sensu stricto or sensu lato. Rather, it represents a distinct lineage in the Mycosphaerellaceae in an unresolved position near Mycosphaerella microsora.