Water turbidity affects the establishment of Neochetina eichhorniae (Warner) (Coleoptera: Curculionidae): Implications for biological control of water hyacinth.

Water hyacinth is the target of nine biological control agents in South Africa including Neochetina eichhorniae (Warner) and Neochetina bruchi (Hustache) (Coleoptera: Curculionidae). These two weevils have also been released against water hyacinth in Rwanda, but failed to control the weed invasion, possibly due to high turbidity in the country's water bodies. This study therefore aimed to investigate the effect of water turbidity on the establishment and performance of N. eichhorniae in Rwanda. Turbidity levels were measured over two seasons in four Rwandan rivers and two lakes. The results were then used to benchmark laboratory trials to test the effect of turbidity on the weevils' development. Water hyacinth plants were maintained at four turbidity levels: Clear water (2 Nephelometric Turbidity Units (NTU): low (85 NTU), medium (600 NTU) and high (1500 NTU). Each treatment plant was inoculated with three N. eichhorniae larvae, while control plants were free of larvae. Plant growth was measured weekly for three months, while adult weevil emergence was recorded from the 56th day of the experiment. The number of adults emerging from the treatment plants grown in the clear water, low, medium and high turbidity levels were 24, 21, 12 and 0, respectively. Larval feeding was greater on plants growing in clear water and the low turbidity, compared to the medium and high turbidity treatments. These results indicate that N. eichhorniae may not establish or perform well in water bodies with high levels of turbidity, which in turn enhances the growth of water hyacinth, allowing compensatory growth for weevil feeding.

Service evaluation of patients' views on the Patients' Concerns Inventory (at diagnosis).

The amount of information wanted by patients after the diagnosis of cancer of the head and neck varies, and valid consent is not possible without information. The Patients' Concerns Inventory (diagnosis) (PCI-D) is a list intended to prompt patients to ask about aspects of their diagnosis and its potential treatments and outcomes. It has not previously been evaluated in clinical practice. Our aim was to assess how often patients recall using it and their satisfaction with both it and the information they received. New patients with oral cancer who attended one consultant's clinic between 2014 and 2015 were evaluated and the response rate was 20/48. A total of 16/18 reported that they were very satisfied or satisfied with it. The Satisfaction with Cancer Information Profile Part B (SCIP-B) showed that the inventory seemed to improve patients' satisfaction with the information that they were given. Further evaluation is required.

How dim is dim? Precision of the celestial compass in moonlight and sunlight.

Prominent in the sky, but not visible to humans, is a pattern of polarized skylight formed around both the Sun and the Moon. Dung beetles are, at present, the only animal group known to use the much dimmer polarization pattern formed around the Moon as a compass cue for maintaining travel direction. However, the Moon is not visible every night and the intensity of the celestial polarization pattern gradually declines as the Moon wanes. Therefore, for nocturnal orientation on all moonlit nights, the absolute sensitivity of the dung beetle's polarization detector may limit the precision of this behaviour. To test this, we studied the straight-line foraging behaviour of the nocturnal ball-rolling dung beetle Scarabaeus satyrus to establish when the Moon is too dim--and the polarization pattern too weak--to provide a reliable cue for orientation. Our results show that celestial orientation is as accurate during crescent Moon as it is during full Moon. Moreover, this orientation accuracy is equal to that measured for diurnal species that orient under the 100 million times brighter polarization pattern formed around the Sun. This indicates that, in nocturnal species, the sensitivity of the optical polarization compass can be greatly increased without any loss of precision.

Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.

Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is beneficial in HF. Despite this promise, the means by which this information might be translated into potential clinical application remains uncertain. Using a recently established cardiac-directed recirculating method of gene delivery, we administered adeno-associated virus 2 (AAV2)/1SERCA2a to sheep with pacing-induced HF. We explored the effects of differing doses of AAV2/1SERCA2a (low 1 x 10(10) d.r.p.; medium 1 x 10(12) d.r.p. and high 1 x 10(13) d.r.p.) in conjunction with an intra-coronary delivery group (2.5 x 10(13) d.r.p.). At the end of the study, haemodynamic, echocardiographic, histopathologic and molecular biologic assessments were performed. Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, (+d P/d t(max); low dose -220+/-70, P>0.05; medium dose 125+/-53, P<0.05; high dose 287+/-104, P<0.05) and echocardiographically (fractional shortening: low dose -3+/-2, P>0.05; medium dose 1+/-2, P>0.05; high dose 6.5+/-3.9, P<0.05). In addition to favourable haemodynamic effects, brain natriuretic peptide expression was reduced consistent with reversal of the HF molecular phenotype. In contrast, direct intra-coronary infusion did not elicit any effect on ventricular function. As such, AAV2/1SERCA2a elicits favourable functional and molecular actions when delivered in a mechanically targeted manner in an experimental model of HF. These observations lay a platform for potential clinical translation.

Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma.

This phase II study evaluated vinflunine in chemotherapy naive patients with metastatic melanoma. Vinflunine was administered at 350 mg/m(2) every 3 weeks, but after 9 patients this was reduced to 320 mg/m(2) based on interim analyses of all phase II trials. A partial response was observed in 1 of the first 9 patients (11.1%) treated at 350 mg/m(2), which gives a 3.0% [95% confidence interval (CI): 0.08-15.8] response rate in 33 patients. No change was the best response in 13 patients (39.4%) with progressive disease in 16 (48.5%) and 3 were not evaluable for response. The time to response was 1.4 months and duration was 6 months. At 350 mg/m(2) grade 4 neutropaenia occurred in 3 patients (33.3%) and grade 3 in 2 patients (22.2%) while at 320 mg/m(2) grade 4 neutropaenia occurred in 6 patients (25%) and grade 3 in 3 patients (12.5%) with 2 episodes of grade 3 febrile neutropaenia. Two patients (8.3%) had grade 3 anaemia. These results do not show activity at this dose and schedule for vinflunine in patients with chemotherapy naive metastatic melanoma.

Five-year survival from breast cancer in Western Australia over a decade.

The aim of the present study was to investigate whether 5-year survival of patients with breast cancer in Western Australia has improved over time. We used a population-based study conducted in the State of Western Australia, to identify all cases of invasive breast cancer cases diagnosed in 1989, 1994 and 1999. Information on presentation, investigation and management was extracted from medical records of each case and status at 5 years after date of diagnosis was determined. Comparison of 5-year overall survival for women diagnosed in the three calendar years, and hazard ratios for survival calculated for prognostic variables were measured. We found that survival from breast cancer has improved in Western Australia since 1989. Earlier diagnosis, living in the Perth metropolitan area and use of breast-conserving surgery are associated with better survival, irrespective of year of diagnosis. Further research needs to be carried out to determine the reason for this improvement.

Water stress augments silicon-mediated resistance of susceptible sugarcane cultivars to the stalk borer Eldana saccharina (Lepidoptera: Pyralidae).

Silicon (Si) can improve resistance of plants to insect attack and may also enhance tolerance of water stress. This study tested if Si-mediated host plant resistance to insect attack was augmented by water stress. Four sugarcane cultivars, two resistant (N21, N33) and two susceptible (N26, N11) to Eldana saccharina Walker were grown in a pot trial in Si-deficient river sand, with (Si+) and without (Si-) calcium silicate. To induce water stress, irrigation to half the trial was reduced after 8.5 months. The trial was artificially infested with E. saccharina eggs after water reduction and harvested 66 days later. Silicon treated, stressed and non-stressed plants of the same cultivar did not differ appreciably in Si content. Decreases in numbers of borers recovered and stalk damage were not associated with comparable increases in rind hardness in Si+ cane, particularly in water-stressed susceptible cultivars. Overall, Si+ plants displayed increased resistance to E. saccharina attack compared with Si- plants. Borer recoveries were significantly lower in stressed Si+ cane compared with either stressed Si- or non-stressed Si- and Si+ cane. Generally, fewer borers were recovered from resistant cultivars than susceptible cultivars. Stalk damage was significantly lower in Si+ cane than in Si- cane, for N21, N11 and N26. Stalk damage was significantly less in Si+ combined susceptible cultivars than in Si- combined susceptible cultivars under non-stressed and especially stressed conditions. In general, the reduction in borer numbers and stalk damage in Si+ plants was greater for water-stressed cane than non-stressed cane, particularly for susceptible sugarcane cultivars. The hypothesis that Si affords greater protection against E. saccharina borer attack in water-stressed sugarcane than in non-stressed cane and that this benefit is greatly enhanced in susceptible cultivars is supported. A possible active role for soluble Si in defence against E. saccharina is proposed.

Rural-urban differences in the presentation, management and survival of breast cancer in Western Australia.

From all women diagnosed with invasive breast cancer in 1999 in Western Australia, rural and urban women were compared with regard to mode of detection, tumour characteristics at presentation, diagnostic investigations, treatment and survival. Women from rural areas with breast cancer (n=206, 23%) were less likely to have open biopsy with frozen section (P<0.001), breast-conserving surgery (P<0.001), adjuvant radiotherapy (P=0.004) and hormonal therapy (P=0.03), and were less likely to be treated by a high caseload breast cancer surgeon (P<0.001). Adjusting for age and tumour characteristics, rural women had an increased likelihood of death within 5 years of breast cancer diagnosis (HR 1.62, 95% CI 1.10-2.38). This difference was not significant after adjustment for treatment factors (HR 1.36, 95% CI 0.90-2.04).

Pathology reporting of breast cancer: trends in 1989-1999, following the introduction of mammographic screening in Western Australia.

BACKGROUND: A survey of pathology reporting of breast cancer in Western Australia in 1989 highlighted the need for improvement. The current study documents (1) changes in pathology reporting from 1989 to 1999 and (2) changes in patterns of histopathological prognostic indicators for breast cancer following introduction of mammographic screening in 1989. METHODS: Data concerning all breast cancer cases reported in Western Australia in 1989, 1994 and 1999 were retrieved using the State Cancer Registry, Hospital Morbidity data system, and pathology laboratory records. RESULTS: Pathology reports improved in quality during the decade surveyed. For invasive carcinoma, tumour size was not recorded in 1.2% of pathology reports in 1999 compared with 16.1% in 1989 (p<0.001). Corresponding figures for other prognostic factors were: tumour grade 3.3% and 51.6% (p<0.001), tumour type 0.2% and 4.1% (p<0.001), vascular invasion 3.7% and 70.9% (p<0.001), and lymph node status 1.9% and 4.5% (p = 0.023). In 1999, 5.9% of reports were not in a synoptic/checklist format, whereas all reports were descriptive in 1989 (p<0.001). For the population as a whole, the proportion of invasive carcinomas <1 cm was 20.9% in 1999 compared with 14.5% in 1989 (p<0.001); for tumours <2 cm the corresponding figures were 65.4% and 59.7% (p = 0.013). In 1999, 30.5% of tumours were histologically well-differentiated compared with 10.6% in 1989 (p<0.001), and 61.7% were lymph node negative in 1999 compared with 57.1% in 1989 (p = 0.006). Pure ductal carcinoma in situ (DCIS) constituted 10.9% and 7.9% of total cases of breast carcinoma in 1999 and 1989, respectively (p = 0.01). CONCLUSIONS: Quality of pathology reporting improved markedly over the period, in parallel with adoption of standardised synoptic pathology reports. By 1999, recording of important prognostic information was almost complete. Frequency of favourable prognostic factors generally increased over time, reflecting expected effects of mammographic screening.

Cisplatin and gemcitabine induction chemotherapy followed by concurrent chemoradiotherapy or surgery for locally advanced non-small cell lung cancer.

BACKGROUND: We report a study of induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIA/IIIB non-small cell lung cancer. METHODS: Patients received two cycles of induction chemotherapy with cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. If the disease was resectable [corrected] surgery was followed with two further cycles. If unresectable, patients received cisplatin 100 mg/m(2) day 1, 29 with 5-fluorouracil 1000 mg/m(2) per 24 h continuous infusion for 96 h on days 2-5 and days 30-33 of the radiotherapy administration. Radiation therapy consisted of 63 Gy, 35 fractions, 7 weeks. RESULTS: Of 48 patients, 40% had a partial response to induction chemotherapy. Four of eleven patients with stage IIIA tumours had resectable disease. The remaining seven patients plus 37 with stage IIIB disease had chemoradiotherapy. Response at the completion of all therapy was 62% (IIIA 73%, IIIB 59%). For all patients the median survival was 15.3 months: 1 year and 3 years, 58% and 25%, respectively. Those with IIIB disease responding to induction chemotherapy had significantly superior survival to those that did not respond (37 months vs 11 months; P = 0.005). This remained significant from a landmark at 8 weeks after the start of treatment (P = 0.01). CONCLUSION: These results are equivalent to other studies using induction chemotherapy prior to concurrent chemoradiotherapy. Response to induction chemotherapy may have major prognostic significance.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia.

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p<0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p<0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p=0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p=0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes.

Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.

BACKGROUND: The growth pattern of malignant pleural mesothelioma makes the use of RECIST (response evaluation criteria in solid tumours) response criteria difficult. We have developed and validated Modified RECIST criteria adapted to the growth pattern of malignant pleural mesothelioma. PATIENTS AND METHODS: We evaluated 73 patients from two clinical trials of cisplatin/gemcitabine chemotherapy in malignant pleural mesothelioma. Tumour thickness perpendicular to the chest wall or mediastinum was measured in two positions at three separate levels on thoracic CT scans. The sum of the six measurements defined a pleural unidimensional measure. Bidimensionally measureable lesions were measured unidimensionally as for RECIST. All measurements were added to obtain the total tumour measurement. A reduction of at least 30% on two occasions 4 weeks apart defined a partial response; an increase of 20% over the nadir measurement, progressive disease. The validity of the modified criteria was gauged by evaluating survival and pulmonary function. RESULTS: Response according to these criteria predicted for superior survival (15.1 versus 8.9 months; P = 0.03) and forced vital capacity (FVC) increase during treatment (P <0.0001). A significant correlation between change in linear tumour measurement and FVC was seen (R = 0.63; P = 0.0001). CONCLUSION: These Modified RECIST criteria for tumour response correlate with survival and lung function and can be used to measure outcome in pleural mesothelioma.

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

Phase II trial of ZD0473 as second-line therapy in mesothelioma.

A phase II, open-label, non-comparative, multicentre trial of the platinum analogue ZD0473 as second-line therapy for pleural mesothelioma has been completed. The objectives were to evaluate the activity and tolerability of ZD0473 in patients with relapsed or progressive disease who had received one prior chemotherapy regimen. Forty-seven patients were recruited onto the trial, all aged > 18 years with a life-expectancy > 12 weeks, and World Health Organization (WHO) performance status < or = 2. A starting dose of 120 mg/m2 was administered to 14 patients, six of whom subsequently had their dose escalated to 150 mg/m2. Thirty-three patients received a starting dose of 150 mg/m2. In total, 147 treatment cycles were administered (median number of cycles 3 [range 1-6]). The main toxicity of ZD0473 was haematological (thrombocytopenia) and the most common non-haematological adverse event was nausea. There was no clinically significant nephro-, neuro-, or oto-toxicity. Of the 43 patients evaluable for response, 12% had a minor response (defined by a reduction in lesion size > or = 10% but < 50%), 44% had stable disease, 40% had disease progression, and two patients died before an objective response could be assigned. Median time to progression and death in evaluable patients was 77 days (95% confidence interval [CI]: 44, 105 days) and 203 days (95% CI: 165, 277 days), respectively. In conclusion, although ZD0473 demonstrated a manageable tolerability profile, no complete or partial responses were seen in second-line treatment of mesothelioma. This trial also demonstrates that clinical trials in second-line mesothelioma patients are feasible.

Phased-Array intracardiac echocardiography to guide radiofrequency ablation in the left atrium and at the pulmonary vein ostium.

INTRODUCTION: We sought to evaluate the utility of a phased-array intracardiac echocardiography (ICE) device to identify left atrial (LA) and pulmonary vein (PV) anatomy; accurately guide radiofrequency ablation (RFA) to the right or left PV ostium and LA appendage (LAA); and evaluate PV blood flow before and after RFA using Doppler parameters. METHODS AND RESULTS: Twelve adult sheep were anesthetized and an Acuson 10-French, 7-MHz ICE transducer introduced via the internal jugular vein into the right atrium. The LA was imaged and PV anatomy and blood flow documented using two-dimensional and pulsed-wave Doppler. Mean LA dimensions were 4.6 +/- 0.4 x 3.5 +/- 0.5 cm; mean single right and left main PV ostium diameters were 1.5 +/- 0.2 and 1.3 +/- 0.3 cm; and mean right and left PV first-order branch diameters were 0.8 +/-0.2 and 0.6 +/- 0.1 cm. Mean PV maximum inflow velocity for the right PV were 0.30 +/- 0.05 m/sec and for the left PV were 0.35 +/- 0.04 m/sec. The PV ostia and LAA could be targeted accurately for RFA using ICE guidance. At pathologic evaluation, the mean distance of the lesion center to the right or left PV-LA junction was 3.0 +/- 2.0 mm. The mean distance of the lesion center to the posterior margin of the LAA was <4 mm in all cases. There was no significant increase in PV maximum inflow velocity or decrease in PV diameter following RFA at the PV ostium. Absence of PV obstruction was confirmed at pathology. CONCLUSION: Phased-array ICE allows detailed assessment of LA and PV anatomy when imaged from the right atrium; accurate guidance of RFA to the PV ostium and LAA; and immediate evaluation of PV patency after RFA.

The effect of mammographic screening on invasive breast cancer in Western Australia.

OBJECTIVE: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. DESIGN: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. SETTING: Western Australia (population 1.8 million). Active recruitment of women aged 50-69 years for mammographic screening began in 1989. MAIN OUTCOME MEASURES: Size and stage of invasive breast cancers at diagnosis. RESULTS: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100,000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of "impalpable" tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumors that were negative on assays for oestrogen and progesterone receptors. CONCLUSIONS: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.