The role of selection and historical factors in driving population differentiation along an elevational gradient in an island bird.

Adaptation to local environmental conditions and the range dynamics of populations can influence evolutionary divergence along environmental gradients. Thus, it is important to investigate patterns of both phenotypic and genetic variations among populations to reveal the respective roles of these two types of factors in driving population differentiation. Here, we test for evidence of phenotypic and genetic structure across populations of a passerine bird (Zosterops borbonicus) distributed along a steep elevational gradient on the island of Réunion. Using 11 microsatellite loci screened in 401 individuals from 18 localities distributed along the gradient, we found that genetic differentiation occurred at two spatial levels: (i) between two main population groups corresponding to highland and lowland areas, respectively, and (ii) within each of these two groups. In contrast, several morphological traits varied gradually along the gradient. Comparison of neutral genetic differentiation (FST ) and phenotypic differentiation (PST ) showed that PST largely exceeds FST at several morphological traits, which is consistent with a role for local adaptation in driving morphological divergence along the gradient. Overall, our results revealed an area of secondary contact midway up the gradient between two major, cryptic, population groups likely diverged in allopatry. Remarkably, local adaptation has shaped phenotypic differentiation irrespective of population history, resulting in different patterns of variation along the elevational gradient. Our findings underscore the importance of understanding both historical and selective factors when trying to explain variation along environmental gradients.

Extremely reduced dispersal and gene flow in an island bird.

The Réunion grey white-eye, Zosterops borbonicus, a passerine bird endemic to Réunion Island in the Mascarene archipelago, represents an extreme case of microgeographical plumage colour variation in birds, with four distinct colour forms occupying different parts of this small island (2512 km(2)). To understand whether such population differentiation may reflect low levels of dispersal and gene flow at a very small spatial scale, we examined population structure and gene flow by analysing variation at 11 microsatellite loci among four geographically close localities (<26 km apart) sampled within the distribution range of one of the colour forms, the brown-headed brown form. Our results revealed levels of genetic differentiation that are exceptionally high for birds at such a small spatial scale. This strong population structure appears to reflect low levels of historical and contemporary gene flow among populations, unless very close geographically (<10 km). Thus, we suggest that the Réunion grey white-eye shows an extremely reduced propensity to disperse, which is likely to be related to behavioural processes.

Learning, techniques, and complications of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline.

This article is the second of a two-part publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided Trucut biopsy. The first part (the Clinical Guideline) focused on the results obtained with EUS-guided sampling, and the role of this technique in patient management, and made recommendations on circumstances that warrant its use. The current Technical Guideline discusses issues related to learning, techniques, and complications of EUS-guided sampling, and to processing of specimens. Technical issues related to maximizing the diagnostic yield (e.g., rapid on-site cytopathological evaluation, needle diameter, microcore isolation for histopathological examination, and adequate number of needle passes) are discussed and recommendations are made for various settings, including solid and cystic pancreatic lesions, submucosal tumors, and lymph nodes. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling. A two-page executive summary of evidence statements and recommendations is provided.

Locally asymmetric introgressions between subspecies suggest circular range expansion at the Antirrhinum majus global scale.

Assessing processes of geographic expansion in contact zones is a crucial step towards an accurate prediction of the evolution of species genetic diversity. The geographic distribution of cytonuclear discordance often reflects genetic introgression patterns across a species geographic range. Antirrhinum majus pseudomajus and A. m. striatum are two interfertile subspecies that occupy nonoverlapping areas but enter in contact in many locations at the margin of their geographic distribution. We found that genetic introgression between both subspecies was asymmetric at the local scale and geographically oriented in opposite directions at both ends of their contact zone perimeter in the Pyrenees. Our results suggest that the geographic expansion of A. majus subspecies was circular around the perimeter of their contact zone and pinpoint the need to integrate different spatial scales to unravel complex patterns of species geographic expansion.

Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling in gastroenterology, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB), of submucosal tumors, diffuse esophageal/gastric wall thickening, pancreatic solid masses and cystic-appearing lesions, mediastinal lesions unrelated to lung or esophageal cancer, cancer of the esophagus, stomach, and rectum, lymph nodes of unknown origin, adrenal gland masses, and focal liver lesions. False-positive cytopathological results and needle tract seeding are also discussed. The present Clinical Guideline describes the results of EUS-guided sampling in the different clinical settings, considers the role of this technique in patient management, and makes recommendations on circumstances that warrant its use. A two-page executive summary of evidence statements and recommendations is provided. A separate Technical Guideline describes the general technique of EUS-guided sampling, particular techniques to maximize the diagnostic yield depending on the nature of the target lesion, and sample processing. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling.

Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

BACKGROUND AND STUDY AIMS: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. PATIENTS AND METHODS: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. RESULTS: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CONCLUSIONS: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Are Q(ST)-F(ST) comparisons for natural populations meaningful?

Comparisons between putatively neutral genetic differentiation amongst populations, F(ST), and quantitative genetic variation, Q(ST), are increasingly being used to test for natural selection. However, we find that approximately half of the comparisons that use only data from wild populations confound phenotypic and genetic variation. We urge the use of a clear distinction between narrow-sense Q(ST), which can be meaningfully compared with F(ST), and phenotypic divergence measured between populations, P(ST), which is inadequate for comparisons in the wild. We also point out that an unbiased estimate of Q(ST) can be found using the so-called 'animal model' of quantitative genetics.

Miniprobe EUS in the pretherapeutic assessment of early esophageal neoplasia.

BACKGROUND AND STUDY AIMS: The high-frequency endosonography miniprobe has been advocated prior to endoscopic treatment of superficial esophageal neoplasm. We conducted a retrospective study, which summarized our clinical experience with various miniprobe techniques in the assessment of early squamous cell carcinoma (SCC) and superficial adenocarcinoma on Barrett's mucosa (SAB). PATIENTS AND METHODS: A total of 106 superficial and naive esophageal lesions were included in this series (52 SAB, 54 SCC). The results of the miniprobe staging were compared with pathology in order to determine the accuracy of this technique in differentiating mucosal from submucosal infiltration. Secondary aims were a comparison between the frequencies (20- vs. 30-MHz) and coupling methods (water-filled lumen vs. balloon-sheathed catheter) used. RESULTS: Overall accuracy, sensitivity, and specificity to differentiate T1sm from T1 m tumors were 73.5 %, 62 %, and 76.5 %, respectively. Overdiagnosis occurred in 18.6 % of the lesions. No statistically significant difference was found in the accuracy of the miniprobe staging between the two lesion types (SCC and SAB) ( P = 0.65), and results were significantly poorer in the distal part of the esophagus ( P = 0.00039). No significant difference was found between the two frequencies ( P = 0.51). Water-filled lumen proved to be superior to the balloon-sheathed catheter ( P = 0.015). CONCLUSION: High-frequency miniprobe examination has a limited accuracy in the detection of submucosal invasion in early esophageal cancer. Further improvements in acoustic coupling and ultrasound technique are required to improve the miniprobe accuracy before its implementation into clinical routine.

Vestigial retrorectal cystic tumors in adults: a review of 30 cases.

OBJECTIVES: Retrorectal tumors are uncommon. This is a report on a series of vestigial retrorectal cystic tumors in adults that were surgically removed at two medical centers in France. We also assessed the significance of imaging and, in particular, magnetic resonance imaging (MRI) in the management of these lesions. METHODS: The medical files of adult patients operated on for vestigial retrorectal cystic tumors over the past 15 years were retrospectively studied and, in particular, the radiological studies, the treatment and the histopathology. RESULTS: Thirty patients underwent surgery for vestigial retrorectal cystic tumor. A preoperative diagnosis was possible in almost all cases. The surgical procedure was justified by preoperative imaging and included the transanal approach (three cases), posterior approach (23 cases), anterior approach (two cases) and combined posterior and anterior approach (two cases). Imaging can identify a multilobular lesion that may require the use of a coccygeal approach to achieve complete resection. During a mean follow-up of 3.2 years (range 0.5-15 years), two patients had a local recurrence (successfully surgically removed), and a further two patients were lost to follow-up. Only one lesion was malignant. CONCLUSIONS: Preoperative imaging, and especially magnetic resonance imaging, enables both a specific diagnosis and the selection of the optimal surgical procedure for the treatment of vestigial retrorectal cystic tumors in adults.

[Bile duct involvement in autoimmune pancreatitis: classification and treatment]. / Atteinte biliaire au cours d'une pancréatite auto-immune: quel cadre nosologique et quel traitement?

Autoimmune pancreatitis is a rare disease characterized by inflammation of the pancreatic parenchyma, irregular narrowing of the pancreatic duct, periductal lymphoplasmacytic infiltration and fibrosis at histological examination, the presence of autoantibodies and hypergammaglobulinemia, as well as the possible association of cholangitis and other autoimmune diseases. There is a favorable response to steroid therapy. We report the case of a patient with autoimmune pancreatitis with bile duct involvement and peripheral eosinophilia, requiring long-term immunosuppressant treatment. The diagnosis of a diffuse form of AIP was made without direct histological evidence and based on indirect imaging, clinical and laboratory findings in an autoimmune context. The histological and imaging studies of bile duct involvement and the favourable response to steroids were additional arguments.

Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells.

CD14-positive monocytes obtained from human peripheral blood were cultured with GM-CSF and IL-4. During the early culture phase immature dendritic cells (DCs) developed which not only expressed CD1a, HLA-DR and CD86, but also expressed the endothelial cell markers von Willebrand factor (vWF), VE-cadherin and VEGF receptors Flt-1 and Flt-4. Further maturation of DCs was achieved by prolonged cultivation with TNFalpha. These cells showed typical DC morphology and like professional antigen-presenting cells (APCs) expressed CD83 and high levels of HLA-DR and CD86. However, if immature DCs were grown with VEGF, bFGF and IGF-1 on fibronectin/vitronectin-coated culture dishes, a marked change in morphology into caudated or oval cells occurred. In the presence of these angiogenic growth factors the cultured cells developed into endothelial-like cells (ELCs), characterized by increased expression of vWF, KDR and Flt-4 and a disappearance of CD1a and CD83. Addition of IL-4 and Oncostatin M also increased VE-cadherin expression, and the loosely adherent cells formed clusters, cobblestones and network-like structures. vWF- expressing ELCs mainly originated from CD1a-positive cells, and VEGF was responsible for the decrease in the expression of the DC markers CD1a and CD83. In mixed leukocyte cultures, mature DCs were more potent APCs than ELCs. Moreover, Ac-LDL uptake, and the formation of tubular structures on a plasma matrix was restricted to ELCs. These results suggest that in the presence of specific cytokines immature DCs have the potential to differentiate along different lineages, i.e. into a cell type resembling ELCs.

[Situation of sultopride among present-day neuroleptics]. / Essai de situation du sultopride parmi les neuroleptiques actuels

The authors report preliminary clinical investigations about sultopride, a new substituted benzamid, related to sulpiride. The drug was administered to thirty-nine hospitalized psychotic patients. A very powerful and constant efficacy of sultopride was observed in 11 manic and hypomanic typical syndroms: excitation was controlled between the first and third day, with oral doses of 1,200-1,800 mg. But thymical inversion was observed in 8 cases (3 light anxious states and 5 typical melancholic syndroms). Besides, interesting improvements were obtained in atypical excitation disorders, chronic hallucinatory delusions, acute oniric and confusional states, schizophrenia and chronic alcoholism. Side-effects were frequent: extrapyramidal syndroms, often requiring antiparkinsonian correctors, somnolence, asthenia, and above all (in 30 percent of cases) psychical side-effects, consisting in depressive and anxious modifications of mood, even apart from manic-melancholic psychosis. This psychotropic depressive effect appears as very interesting theoretically, and justifies further enquiry.

[Endosonography in gastroenterology. Update in 1989]. / L'endosonographie en gastro-entérologie. Le point en 1989.

Endosonography consists of exploring the gastrointestinal wall and surrounding tissue with the aid of an ultrasound transducer introduced into the gastrointestinal lumen. High frequency ultrasound (more than 7 MHz) is used and provides high definition imaging. Its principal role is in oncology, and more particularly in the assessment of tumor extension. Regardless of whether it is the rectum, esophagus or stomach being considered, it is possible to predict the depth of tumor invasion in the wall in more than 80% of cases. The determination of invasion of adjacent organs is still somewhat imprecise. Endosonography provides better analysis of lymph nodes than CT scan (70 to 75% precision) and improvements will occur with better description of the criteria of malignancy. It appears interesting for the evaluation of pancreatic and biliary tumors and for follow-up of patients already treated for gastrointestinal cancer. Among its other indications, some have been well established (gastrointestinal submucosal tumors, giant gastropathy) and others require confirmation (villous tumors of the rectum, gastric ulcer).

[Respiratory function and alveolar biological changes under the effect of CDP-choline in pulmonary interstitial pathology: pulmonary fibrosis and sarcoidosis]. / Etude des modifications fonctionnelles respiratoires et biologiques alvéolaires sous l'effet de la CDP-choline dans le cadre de la pathologie interstitielle pulmonaire: fibroses pulmonaires et sarcoïdoses.

Various anomalies of pulmonary surfactant have been described in relation to acute respiratory distress syndromes, hypersensitivity lung disease and pulmonary sarcoidosis. Phosphatidylcholine (PC) is the essential phospholipid component of pulmonary surfactant. Cytidine diphosphocholine (CDP-choline) is an essential intermediary in the biosynthesis of PC. The authors studied two groups of patients: one group consisted of diffuse interstitial pulmonary fibrosis and the other consisted of pulmonary sarcoidosis with parenchymal involvement. They observed quantitative and qualitative abnormalities of the phospholipid fractions of surfactant and more particularly of PC. The finding of a marked decrease in this phospholipid, especially in the cases of pulmonary fibrosis, justified the study of the therapeutic effects of CDP-choline. After one month of treatment with this substance, at a dose of 1 g I.M. per day, the PC fraction had returned to normal and, at the same time, there was an improvement in the PaO2 at rest and after exercise. Long term administration of CDP-choline appears to be valuable in the maintenance of the phospholipid equilibrium of pulmonary surfactant and in the improvement of the quality of alveolar gas exchange.

Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study.

OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung. METHODS: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL. RESULTS: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). SAFETY: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). LIMITATIONS: Potential bias could not be excluded due to the study's observational nature. CONCLUSIONS: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

A final analysis from the CHOICE study examining darbepoetin alfa use for chemotherapy-induced anaemia in current European clinical practice.

OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA). METHODS: Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL after 9 weeks' DA treatment. RESULTS: The full analysis set (FAS) comprised 1887 patients (mean ± SD age 62.4 ± 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9-<10 g/dL (n = 770); 10-<11 g/dL (n = 695); ≥11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL, respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels ≥10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups, respectively. Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study's observational nature. CONCLUSIONS: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL.

Current practice of darbepoetin alfa in the management of haemoglobin levels in cancer patients undergoing chemotherapy - data from the CHOICE study.

OBJECTIVE: To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally. METHODS: This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected. RESULTS: Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10 g/dL. At week 9, 426 (33%) patients had a Hb level of 10-12 g/dL, 165 (13%) of >12 g/dL, 226 (18%) of <10 g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10-12 g/dL. For patients with a baseline Hb of <10 g/dL, the Kaplan-Meier (K-M) percentage of patients with Hb levels ≥10 g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K-M% of patients with Hb levels >13 g/dL from week 1 to EOTP was 10%. The K-M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses. CONCLUSIONS: This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13 g/dL were infrequent. Limitations are related to the observational nature of this study.