Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

Combination of CFD and DOE to analyze and improve the mass flow rate in urinary catheters

The urinary catheter is a thin plastic tube that has been designed to empty the bladder artificially, effortlessly, and with minimum discomfort. The current CH14 male catheter design was examined with a view to optimizing the mass flow rate. The literature imposed constraints to the analysis of the urinary catheter to ensure that a compromise between optimal flow, patient comfort, and everyday practicality from manufacture to use was achieved in the new design. As a result a total of six design characteristics were examined. The input variables in question were the length and width of eyelets 1 and 2 (four variables), the distance between the eyelets, and the angle of rotation between the eyelets. Due to the high number of possible input combinations a structured approach to the analysis of data was necessary. A combination of computational fluid dynamics (CFD) and design of experiments (DOE) has been used to evaluate the "optimal configuration." The use of CFD couple with DOE is a novel concept, which harnesses the computational power of CFD in the most efficient manner for prediction of the mass flow rate in the catheter. Copyright © 2009 by ASME.

Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival

Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of lowdose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 days every 6 weeks or clofarabine 20 mg/m2 on days 1 to 5, both for up to 4 courses. These patients had more adverse demographics than contemporaneous intensively treated patients. The overall remission rate was 28%, and 2-year survival was 13%. Clofarabine significantly improved complete remission (22% vs 12%; hazard ratio [HR] 5 0.47 [0.28-0.79]; P 5 .005) and overall response (38% vs 19%; HR 5 0.41 [0.26-0.62]; P < .0001), but there was no difference in overall survival, explained by poorer survival in the clofarabine patients who did not gain complete remission and also following relapse. Clofarabine was more myelosuppressive and required more supportive care. Although clofarabine doubled remission rates, overall survival was not improved overall or in any subgroup. The treatment of patients of the type treated here remains a major unmet need. This trial was registered at www.clinicaltrials.gov as #ISRCTN 11036523.

Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/µm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.

Orthogonal space-time block coded rate-adaptive modulation with outdated feedbasck

Abstract-Channel state information (CSI) at the transmitter can be used to adapt transmission rate or antenna gains in multi-antenna systems. We propose a rate-adaptive M-QAM scheme equipped with orthogonal space-time block coding with simple outdated, finite-rate feedback over independent flat fading channels. We obtain closed-form expressions for the average BER and throughput for our scheme, and analyze the effects of possibly delayed feedback on the performance gains. We derive optimal switching thresholds maximizing the average throughput under average and outage BER constraints with outdated feedback. Our numerical results illustrate the immunity of our optimal thresholds to delayed feedback.

Economies of scaling: More evidence that allometry of metabolism is linked to activity, metabolic rate and habitat

Organismal metabolic rates influence many ecological processes, and the mass-specific metabolic rate of organisms decreases with increasing body mass according to a power law. The exponent in this equation is commonly thought to be the three-quarter-power of body mass, determined by fundamental physical laws that extend across taxa. However, recent work has cast doubt as to the universality of this relationship, the value of 0.75 being an interspecies 'average' of scaling exponents that vary naturally between certain boundaries. There is growing evidence that metabolic scaling varies significantly between even closely related species, and that different values can be associated with lifestyle, activity and metabolic rates. Here we show that the value of the metabolic scaling exponent varies within a group of marine ectotherms, chitons (Mollusca: Polyplacophora: Mopaliidae), and that differences in the scaling relationship may be linked to species-specific adaptations to different but overlapping microhabitats. Oxygen consumption rates of six closely related, co-occurring chiton species from the eastern Pacific (Vancouver Island, British Columbia) were examined under controlled experimental conditions. Results show that the scaling exponent varies between species (between 0.64 and 0.91). Different activity levels, metabolic rates and lifestyle may explain this variation. The interspecific scaling exponent in these data is not significantly different from the archetypal 0.75 value, even though five out of six species-specific values are significantly different from that value. Our data suggest that studies using commonly accepted values such as 0.75 derived from theoretical models to extrapolate metabolic data of species to population or community levels should consider the likely variation in exponents that exists in the real world, or seek to encompass such error in their models. This study, as in numerous previous ones, demonstrates that scaling exponents show large, naturally occurring variation, and provides more evidence against the existence of a universal scaling law. © 2012 Elsevier B.V.

The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia:results from the LRF AML14 and NCRI AML16 pick-a-winner comparison

The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32-0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.

Management of Bartholin's gland carcinoma using high-dose-rate interstitial brachytherapy boost

To describe the patterns of use, clinical outcomes, and dose-volume histogram parameters of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the management of Bartholin's gland cancer.