Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events

A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis

The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Successful treatment of Sydenham's chorea with intravenous immunoglobulin

We present a case of a 10-year-old girl diagnosed with Sydenham's chorea. Despite treatment with haloperidol and valproic acid for 2 weeks and antibiotics for 5 days, her symptoms continued to worsen. She became severely impaired in daily functioning, as she could barely speak or walk, experienced major feeding difficulties and required help with all daily activities. She was treated with intravenous immunoglobulin (IVIG). Within 4 days, her symptoms started to improve and after 1-month she had fully recovered. This case reminds us that Sydenham's chorea can result in major functional impairment. There is some evidence on the beneficial effect of IVIG in the treatment of Sydenham's chorea, as is evident in our case. Therefore, IVIG should be considered as a treatment option in patients with severe chore

Improving MFI-UF constant flux to more accurately predict particulate fouling in RO systems: Quantifying the effect of membrane surface porosity

This study aimed to quantify the effect of membrane surface porosity on particulate fouling predicted by the MFI-UF method at constant flux. Firstly, the surface porosity of polyethersulfone UF membranes (5–100 kDa) was determined using ultra-high resolution SEM. Thereafter, the MFI-UF was measured using suspensions of polystyrene particles (75 nm), which were pre-washed to remove surfactant and particle fractions smaller than the pores of MFI-UF membranes, thus ensuring complete retention of particles during MFI-UF measurements. Consequently, the MFI-UF values of washed polystyrene particle suspensions were independent of the pore size and depended only on the surface porosity of MFI-UF membrane. The results showed that the membrane surface porosity decreased with MWCO from 10.5% (100 kDa) to 0.6% (5 kDa), and consequently the MFI-UF increased from 3700 to 8700 s/L2, respectively. This increase in MFI-UF was attributed to the non-uniform distribution of membrane pores, which is exacerbated as surface porosity decreases. Consequently, preliminary correction factors of 0.4–1.0 were proposed for MFI-UF measured with UF membranes in the range 5–100 kDa. Finally, the surface porosity correction was applied to predict particulate fouling in a full-scale RO plant. However, additional research is required to establish correction factors for different types of feed water.Sanitary Engineerin