Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis

BACKGROUND: To determine whether the dose-volume histograms (DVH's) for the rectum and bladder constructed using biological-effective dose (BED-DVH's) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVH's (C-DVH's). METHODS: The charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVH's and BED-DVH's of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVH's were computed: (a) δ(AUC )= (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δ(V60 )= (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient). RESULTS: As expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVH's – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δ(AUC )was higher for the BED-DVH's than for the C-DVH's – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δ(V60 )was also higher for the BED-DVH's than for the C-DVH's – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder. CONCLUSIONS: When considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVH's for the rectum and bladder correlate better with late toxicity than C-DVH's and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer

A mechanistic framework for auxin dependent Arabidopsis root hair elongation to low external phosphate

Phosphate (P) is an essential macronutrient for plant growth. Roots employ adaptive mechanisms to forage for P in soil. Root hair elongation is particularly important since P is immobile. Here we report that auxin plays a critical role promoting root hair growth in Arabidopsis in response to low external P. Mutants disrupting auxin synthesis (taa1) and transport (aux1) attenuate the low P root hair response. Conversely, targeting AUX1 expression in lateral root cap and epidermal cells rescues this low P response in aux1. Hence auxin transport from the root apex to differentiation zone promotes auxin-dependent hair response to low P. Low external P results in induction of root hair expressed auxin-inducible transcription factors ARF19, RSL2, and RSL4. Mutants lacking these genes disrupt the low P root hair response. We conclude auxin synthesis, transport and response pathway components play critical roles regulating this low P root adaptive response

Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin

In bone disorders infections are common. The concentration of majority of antibiotics is very low in the bone tissue. A high local dose can be obtained from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite nanoparticles as a carrier for ciprofloxacin drug delivery system. The ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized using X-ray diffraction, Transmission electron microscopy and inductively coupled plasma optical emission spectrometry. They were loaded with ciprofloxacin using optimized drug loading parameters. Drug loading, in vitro drug release and antimicrobial activity were analyzed. The influence of zinc on the controlled release of ciprofloxacin was analyzed. The results show that the presence of zinc increases the drug release percentage and that the drug was released in a controlled manner

The impact of pesticide suicide on the geographic distribution of suicide in Taiwan: a spatial analysis

<p>Abstract</p> <p>Background</p> <p>Pesticide self-poisoning is the most commonly used suicide method worldwide, but few studies have investigated the national epidemiology of pesticide suicide in countries where it is a major public health problem. This study aims to investigate geographic variations in pesticide suicide and their impact on the spatial distribution of suicide in Taiwan.</p> <p>Methods</p> <p>Smoothed standardized mortality ratios for pesticide suicide (2002-2009) were mapped across Taiwan's 358 districts (median population aged 15 or above = 27 000), and their associations with the size of agricultural workforce were investigated using Bayesian hierarchical models.</p> <p>Results</p> <p>In 2002-2009 pesticide poisoning was the third most common suicide method in Taiwan, accounting for 13.6% (4913/36 110) of all suicides. Rates were higher in agricultural East and Central Taiwan and lower in major cities. Almost half (47%) of all pesticide suicides occurred in areas where only 13% of Taiwan's population lived. The geographic distribution of overall suicides was more similar to that of pesticide suicides than non-pesticide suicides. Rural-urban differences in suicide were mostly due to pesticide suicide. Areas where a higher proportion of people worked in agriculture showed higher pesticide suicide rates (adjusted rate ratio [ARR] per standard deviation increase in the proportion of agricultural workers = 1.58, 95% Credible Interval [CrI] 1.44-1.74) and overall suicide rates (ARR = 1.06, 95% CrI 1.03-1.10) but lower non-pesticide suicide rates (ARR = 0.91, 95% CrI 0.87-0.95).</p> <p>Conclusion</p> <p>Easy access to pesticides appears to influence the geographic distribution of suicide in Taiwan, highlighting the potential benefits of targeted prevention strategies such as restricting access to highly toxic pesticides.</p

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

New species of Ptychozoon (Sauria: Gekkonidae) from the Nicobar Archipelago, Indian Ocean

A new species of Ptychozoon is described from the central portion of the Nicobar Archipelago, Bay of Bengal, India. It has been formerly referred to P. kuhli, a species widely distributed in Sundaland. Ptychozoon nicobarensis sp. nov. reaches an SVL of 100.3 mm, and is diagnosable from congeneric species in showing the following combination of characters: dorsum with a tan vertebral stripe, lacking dark transverse bars; supranasals in contact; cutaneous expansions on sides of head; absence of predigital notch in preantebrachial cutaneous expansion; imbricate parachute support scales; four irregular rows of low, rounded enlarged scales on dorsum; 20-29 scales across widest portion of tail terminus; three indistinct chevrons on dorsum; 7-11 pairs of preanal pores; femoral pores absent; tail with an expanded terminal flap and weak lobe fusion at proximal border of tail terminus. The curious distribution of the new species, centred around the central Nicobars is speculated to be the result of competition with and/or predation by large gekkonid species, to the north (Gekko verreauxi) and south (G. smithii) of the group of islands occupied by the new Ptychozoon from the central Nicobars