151 research outputs found
Analysis of Electric Field Strength for Planning Indoor 5.8 GHz Wireless Networks
Understanding radio channel path characteristics is a very important factor for ensuring quality of service and high data rates for indoor wireless communication systems. Obstacles such as human occupants, doors, walls, windows, etc. all have a significant impact on received signals strengths and will contribute to fading, multipath and shadowing effects. This paper studies the effects of changes within a building, such as opening and closing doors, and the movement and number of human occupants, on indoor signal propagation at 5.8 GHz. The effects of different obstacles inside the rooms are compared and highlight which has the most significant effect on the received electric field strength
LIM kinase function and renal growth: potential role for LIM kinases in fetal programming of kidney development
Aims
Maternal dietary restriction during pregnancy impairs nephron development and results in offspring with fewer nephrons. Cell turnover in the early developing kidney is altered by exposure to maternal dietary restriction and may be regulated by the LIM-kinase family of enzymes. We set out to establish whether disturbance of LIM-kinase activity might play a role in the impairment of nephron formation.
Main methods
E12.5 metanephric kidneys and HK2 cells were grown in culture with the pharmacological LIM-kinase inhibitor BMS5. Organs were injected with DiI, imaged and cell numbers measured over 48 h to assess growth. Cells undergoing mitosis were visualised by pH 3 labelling.
Key findings
Growth of cultured kidneys reduced to 83% of controls after exposure to BMS5 and final cell number to 25% of control levels after 48 h. Whilst control and BMS5 treated organs showed cells undergoing mitosis (100 ± 11 cells/field vs 113 ± 18 cells/field respectively) the proportion in anaphase was considerably diminished with BMS5 treatment (7.8 ± 0.8% vs 0.8 ± 0.6% respectively; P < 0.01). This was consistent with effects on HK2 cells highlighting a severe impact of BMS5 on formation of the mitotic spindle and centriole positioning. DiI labelled cells migrated in 100% of control cultures vs 0% BMS5 treated organs. The number of nephrogenic precursor cells appeared depleted in whole organs and formation of new nephrons was blocked by exposure to BMS5.
Significance
Pharmacological blockade of LIM-kinase function in the early developing kidney results in failure of renal development. This is likely due to prevention of dividing cells from completion of mitosis with their resultant loss
Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial
Background: Peri-operative chemotherapy and surgery is a standard of care for patients with resectable oesophagogastric adenocarcinoma. Bevacizumab, a monoclonal antibody against VEGF, improves the proportion of patients responding to treatment in advanced gastric cancer. We aimed to assess the safety and efficacy of adding bevacizumab to peri-operative chemotherapy in patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Methods: In this multicentre, randomised, open-label phase 2–3 trial, we recruited patients aged 18 years and older with histologically proven, resectable oesophagogastric adenocarcinoma from 87 UK hospitals and cancer centres. We randomly assigned patients 1:1 to receive peri-operative epirubicin, cisplatin, and capecitabine chemotherapy or chemotherapy plus bevacizumab, in addition to surgery. Patients in the control group (chemotherapy alone) received three pre-operative and three post-operative cycles of epirubicin, cisplatin, and capecitabine chemotherapy: 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 and 1250 mg/m2 oral capecitabine on days 1–21. Patients in the investigational group received the same treatment as the control group plus 7·5 mg/kg intravenous bevacizumab on day 1 of every cycle of chemotherapy and for six further doses once every 21 days following chemotherapy, as maintenance treatment. Randomisation was done by means of a telephone call to the Medical Research Council Clinical Trials Unit, where staff used a computer programme that implemented a minimisation algorithm with a random element to establish the allocation for the patient at the point of randomisation. Patients were stratified by chemotherapy centre, site of tumour, and tumour stage. The primary outcome for the phase 3 stage of the trial was overall survival (defined as the time from randomisation until death from any cause), analysed in the intention-to-treat population. Here, we report the primary analysis results of the trial; all patients have completed treatment and the required number of primary outcome events has been reached. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 46020948, and with ClinicalTrials.gov, number NCT00450203. Findings: Between Oct 31, 2007, and March 25, 2014, 1063 patients were enrolled and randomly assigned to receive chemotherapy alone (n=533) or chemotherapy plus bevacizumab (n=530). At the time of analysis, 508 deaths were recorded (248 in the chemotherapy alone group and 260 in the chemotherapy plus bevacizumab group). 3-year overall survival was 50·3% (95% CI 45·5–54·9) in the chemotherapy alone group and 48·1% (43·2–52·7) in the chemotherapy plus bevacizumab group (hazard ratio [HR] 1·08, 95% CI 0·91–1·29; p=0·36). Apart from neutropenia no other toxic effects were reported at grade 3 or worse severity in more than 10% of patients in either group. Wound healing complications were more prevalent in the bevacizumab group, occurring in 53 (12%) patients in this group compared with 33 (7%) patients in the chemotherapy alone group. In patients who underwent oesophagogastrectomy, post-operative anastomotic leak rates were higher in the chemotherapy plus bevacizumab group (23 [10%] of 233 in the chemotherapy alone group vs 52 [24%] of 220 in the chemotherapy plus bevacizumab group); therefore, recruitment of patients with lower oesophageal or junctional tumours planned for an oesophagogastric resection was stopped towards the end of the trial. Serious adverse events for all patients included anastomotic leaks (30 events in chemotherapy alone group vs 69 in the chemotherapy plus bevacizumab group), and infections with normal neutrophil count (42 events vs 53). Interpretation: The results of this trial do not provide any evidence for the use of bevacizumab in combination with peri-operative epiribicin, cisplatin, and capecitabine chemotherapy for patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Bevacizumab might also be associated with impaired wound healing. Funding: Cancer Research UK, MRC Clinical Trials Unit at University College London, and F Hoffmann-La Roche Limited
Socioeconomic Disadvantage and Child Morbidity: An Australian Longitudinal Study
While an extensive body of literature has demonstrated an association between socioeconomic status and child mortality, there have been relatively few papers which discuss the impact of socioeconomic inequality on child morbidity. This absence of data is partly attributable to methodological problems (need for large samples, the difficulty of assessing morbidity) and partly to the absence of relevant official health statistics. This paper reports results from the Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes. The sample comprises 8556 consecutive pregnancies, of which over 90% were followed up to birth. Of those mothers giving birth, approx. 70% of children were successfully given a health assessment five years after the birth (mothers report of the child's health using a set of standard indicators). The results indicate a consistent pattern with the children of the most socioeconomically disadvantaged mothers manifesting the worst health. Thus children living in socioeconomic disadvantage have a higher rate of health service utilisation, more chronic health problems and poorer dental health. The paper discusses some social policies for redressing these inequalities
Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer : long-term survival results from the STAMPEDE trial
Background
STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
Methods
We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
Results
Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P  0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
Conclusions
The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden
Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.
Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young
Microwave determination of the quasiparticle scattering time in YBa2Cu3O6.95
We report microwave surface resistance (Rs) measurements on two very-high-quality YBa2Cu3O6.95 crystals which exhibit extremely low residual loss at 1.2 K (2-6 μΩ at 2 GHz), a broad, reproducible peak at around 38 K, and a rapid increase in loss, by 4 orders of magnitude, between 80 and 93 K. These data provide one ingredient in the determination of the temperature dependence of the real part of the microwave conductivity, σ1(T), and of the quasiparticle scattering time. The other necessary ingredient is an accurate knowledge of the magnitude and temperature dependence of the London penetration depth, λ(T). This is derived from published data, from microwave data of Anlage, Langley, and co-workers and from, high-quality μSR data. We infer, from a careful analysis of all available data, that λ2(0)/λ2(T) is well approximated by the simple function 1-t2, where t=T/Tc, and that the low-temperature data are incompatible with the existence of an s-wave, BCS-like gap. Combining the Rs and λ(T) data, we find that σ1(T), has a broad peak around 32 K with a value about 20 times that at Tc. Using a generalized two-fluid model, we extract the temperature dependence of the quasiparticle scattering rate which follows an exponential law, exp(T/T0), where T0≊12 K, for T between 15 and 84 K. Such a temperature dependence has previously been observed in measurements of the nuclear spin-lattice relaxation rate. Both the uncertainties in our analysis and the implications for the mechanism of high-temperature superconductivity are discussed
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