[Grand Canyon] 13/8 -32

Kirje 13.8.1932

Berlin 2/3 -32.

Kirje 2.3.1932

Berlin 18/3 -32

Kirje 18.3.1932

[New York] 24/8 -32

Kirje 24.8.1932

Berlin 11/3 -32

Kirje 11.3.1932

Longevity and fecundity of Dichroplus maculipennis (Orthoptera, Acrididae) at non-outbreaking and outbreaking situations

Dichroplus maculipennis is one of the most characteristic and damaging grasshopper species of Argentina, mainly in areas of the Pampas and Patagonia regions. We estimated and compared the longevity and fecundity of adult female D. maculipennis under controlled conditions (30ºC, 14L:10D, 40% RH) from individuals collected as last instar nymphs (VI) in the field and with a known recent history of low and high density conditions. Densities of D. maculipennis at the collecting sites were 0.95 individuals per m² in 2006 and 46 ind/m² in 2009, representing non-outbreaking and outbreaking situations, respectively. Adult female longevity in 2006 (67.96 ± 3.2 days) was significantly higher (p < 0.05) than in 2009 (37.44 ± 1.98 days). The number of egg-pods per female was 3.32 ± 0.44 for 2006 and 1.62 ± 0.26 for 2009. The average fecundity in 2006 (89.29 ± 11.9 eggs/female) was significantly greater (p < 0.05) than that in 2009 (36.27 ± 5.82 eggs/female). While it was observed that the oviposition rate was higher in 2006, this difference was not significant (p > 0.05). The fecundity curves showed that the highest values were at weeks 11 and 13 for the 2006 females, and at week 6 for those of 2009. Since the daily oviposition rate at low and high densities was not significantly different, the diminished fecundity rate at high density is attributable to their reduced longevity.

Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial.

BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION: Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. FUNDING: Amgen.

[New York] 14/7 -32

Kirje 14.7.1932

Mother's attachment representations of their premature infant at 6 and 18 months after birth.

The effects of premature birth on attachment have generally been examined from the infant's perspective. There is a lack of data concerning parental attachment representations toward a premature child. Because of the psychological stress engendered in parents confronted with a premature birth, we hypothesized that their attachment representations would be altered during the first months after the hospital discharge. Fifty families with a premature infant (25-33 gestation weeks) and a control group of 30 families with a full-term infant participated to the study. Perinatal risks were evaluated during hospitalization. To assess mothers' representations of their infant, the Working Model of the Child Interview (WMCI, Zeanah & Benoit, 1995 & Benoit, Zeanah, Parker, Nicholson, & Coolbear, 1997) were administered when their children were 6 and 18 months old. The severity of the perinatal risks was found to have an impact on the mothers' attachment representations. At six months, only 20% of the mothers of a prematurely born infant (30% at 18 months) had secure attachment representations, vs. 53% for the control group (57% at 18 months). Furthermore, mothers of low-risk premature infants more often had disengaged representations, whereas distorted representations were more frequent in the high-risk group of premature children. These findings suggest that the parental response to a premature birth is linked to the severity of postnatal risks. The fact that secure attachment representations are affected in mothers of low-risk infants just as much as they are in mothers of high-risk infants points to the need to conduct further studies aimed at evaluating whether preventive intervention for both low-risk and high-risk premature will be helpful.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.

OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.

Low-pressure environment and remodelling of the forearm vein in Brescia-Cimino haemodialysis access.

BACKGROUND: The aim of the study was to determine which, and to what extent, haemodynamic parameters contribute to the remodelling of the venous limb of the Brescia-Cimino haemodialysis access. METHODS: The dimensions of the radial artery and the venous limb of the haemodialysis access were measured by an echo-tracking technique. In six ESRD patients undergoing primary arteriovenous fistula (AVF) formation, vessel diameter, wall thickness, blood pressure and blood flow were measured after the operation, and at 1 and 3 months follow-up. The contralateral forearm vessels in their native position served as baseline values for comparison. RESULTS: The diameter of the proximal antecubital vein progressively increased over the study period without reaching significant differences (4430, 5041 and 6620 microm at weeks 1, 4 and 12 respectively), whereas the intima-media thickness remained unchanged. The venous dilatation was associated with a reduction of the mean shear stress that culminated after the operation and progressively returned to normal venous values at 3 months (24.5 vs 10.4 dyne/cm(2), P<0.043). Thus the venous limb of the AVF undergoes eccentric hypertrophy as demonstrated by the increase in wall cross-sectional area (4.42 vs 6.32 mm(2) at week 1 vs week 12, P<0.028). At the time of the operation, the blood pressure in the AVF was 151+/-14/92.4+/-11 mmHg vs 49+/-19/24.5+/-6 mmHg (means+/-SEM) for the radial artery and the venous limb of the vascular access, respectively. One year after the operation the blood pressure in the venous limb had not changed: 42+/-14/25.3+/-7 mmHg (means+/-SEM). Under these conditions, the systolo-diastolic diameter changes observed in the radial artery and the antecubital vein were within a similar range at all time points: 56+/-17 vs 90+/-26 microm (means+/-SEM) at week 12. CONCLUSIONS: The increased circumferential stress resulting from the flow-mediated dilatation rather than the elevation of blood pressure appears to represent the main contributing factor to the eccentric hypertrophy of the venous limb of Brescia-Cimino haemodialysis access.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models.Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points.Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination.Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.