Ensuring the safety of animal feed

A general outline is presented of measures for the production of safe animal feed. This is based on the setting of so-called ‘feed safety objectives’ which make use of principles that relate to animal health, animal welfare, legal aspects of farm practices and human food safety objectives for products of animal origin. Particular emphasis will be put on the types of feed used in relation to feedborne animal diseases caused by infectious and chemical agents and on the relationship between animal feed and zoonotic foodborne diseases. In addition the influence of feed on animal welfare will be discussed. To produce safe animal feed, a pro-active control system is advocated. This approach has been very successful in relation to human food and involves the use of ‘good manufacturing practices’ (GMP) and the ‘hazard analysis critical control point’ (HACCP) concept as the main tools. However, it has been shown that the HACCP-system has certain shortcomings. To counteract these shortcomings, product traceability and hazard early-warning systems have been developed and will also be presented

The design & construction of a proton microprobe using a GE PETtrace cyclotron

Title from PDF of title page (University of Missouri--Columbia, viewed on September 10, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Thesis advisor: Dr. Patrick PinheroIncludes bibliographical references.M. S. University of Missouri--Columbia 2012."March 2012"The interaction of fast neutrons with nuclear materials is a topic of fundamental interest in nuclear engineering. Fast neutrons possess the ability to degrade, and in some cases destroy, materials used in nuclear reactor pressure vessels and core internals. Unfortunately, there are very few facilities where extreme fast neutron fluences, approximately 300 displacements per atom, can be reasonably achieved. Research at the University of Missouri Research Reactor (MURR) Cyclotron has focused on increasing the fast neutron flux density by creating a very tight microspot. This thesis focuses on characterizing the MURR cyclotron beam through accurate measurements using a radiochromic film technique, originally developed by Avila-Rodriguez. An ion optics system was designed using SIMION, a finite element analysis software. A quadrupole triplet was used to transport and focus the high-energy beam to a very small point. A cyclotron-based beamline system was constructed at MURR with the following components: drift tubes, a sample chamber with appropriate vacuum components, and associated instrumentation. An acquisition computer and associated electronics were remotely positioned, outside of the cyclotron vault, to control the beamline and ion optics. This remote acquisition system includes a program to record beam current, sample chamber pressure, and the current supplied to the quadrupole magnets. Several safety interlocks were designed to protect workers and equipment. The construction, alignment, and startup of the beam line are presented. Preliminary irradiations of graphite with protons are also presented

Chronic instability of the anterior tibiofibular syndesmosis of the ankle. Arthroscopic findings and results of anatomical reconstruction

<p>Abstract</p> <p>Background</p> <p>The arthroscopic findings in patients with chronic anterior syndesmotic instability that need reconstructive surgery have never been described extensively.</p> <p>Methods</p> <p>In 12 patients the clinical suspicion of chronic instability of the syndesmosis was confirmed during arthroscopy of the ankle. All findings during the arthroscopy were scored. Anatomical reconstruction of the anterior tibiofibular syndesmosis was performed in all patients. The AOFAS score was assessed to evaluate the result of the reconstruction. At an average of 43 months after the reconstruction all patients were seen for follow-up.</p> <p>Results</p> <p>The syndesmosis being easily accessible for the 3 mm transverse end of probe which could be rotated around its longitudinal axis in all cases during arthroscopy of the ankle joint, confirmed the diagnosis. Cartilage damage was seen in 8 ankles, of which in 7 patients the damage was situated at the medial side of the ankle joint. The intraarticular part of anterior tibiofibular ligament was visibly damaged in 5 patients. Synovitis was seen in all but one ankle joint. After surgical reconstruction the AOFAS score improved from an average of 72 pre-operatively to 92 post-operatively.</p> <p>Conclusions</p> <p>To confirm the clinical suspicion, the final diagnosis of chronic instability of the anterior syndesmosis can be made during arthroscopy of the ankle. Cartilage damage to the medial side of the tibiotalar joint is often seen and might be the result of syndesmotic instability. Good results are achieved by anatomic reconstruction of the anterior syndesmosis, and all patients in this study would undergo the surgery again if necessary.</p

The effectiveness of a golf injury prevention program (GRIPP intervention) compared to the usual warm-up in Dutch golfers:protocol design of a randomized controlled trial

BACKGROUND: Sixty million golfers around the world play golf. Golf injuries are most frequently located in the spine, elbow, wrist, hand and shoulder. Those injuries are often seen in golfers with more playing hours and suboptimal swing biomechanics, resulting in overuse injuries. Golfers who do not perform a warm-up or do not warm-up appropriately are more likely to report an injury than those who do. There are several ways to warm-up. It is unclear, which warm-up is most useful for a golfer to perform. Moreover, there is currently no evidence for the effectiveness of a warm-up program for golf injury prevention. We previously have developed the Golf Related Injury Prevention Program (GRIPP) intervention using the Knowledge Transfer Scheme (KTS). We aim to evaluate the effect of the GRIPP intervention on golf-related injuries. The hypothesis is that the GRIPP intervention program will reduce the number of golf-related injuries. METHODS AND DESIGN: The GRIPP study is a two-armed randomized controlled trial. Twenty-eight golf clubs with 11 golfers per club will be randomly allocated to the intervention or control group. The intervention group will perform the GRIPP intervention program, and the control group will perform their warm-up as usual. The GRIPP intervention is conducted with the Knowledge Transfer Scheme framework, which is a systematic process to develop an intervention. The intervention consists of 6 exercises with a maximum total of 10 min. The primary outcome is the overall prevalence (%) of golf injuries measured with the Oslo Sports Trauma Research Center (OSTRC-H) questions on health problems every fortnight. The secondary outcome measures will be exposure to golf and compliance to the intervention program. DISCUSSION: In other sports warm-up prevention programs are effective in reducing the risk of injuries. There are no randomized trials on golf injury prevention. Therefore, an individual unsupervised golf athlete intervention program is conducted which reflects the daily practice of predominantly unsupervised exposure of amateur golfers. TRIAL REGISTRATION: The trial is retrospectively (28 October 2021) registered at the Dutch Trial Register: NL9847 (https://trialsearch.who.int)

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. © 2013 European Molecular Biology Organization

Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103)

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (\u3e 60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability. AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC-MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight (kg). Differences in BuCL between age groups were examined using the Wilcoxon rank sum test. One hundred and eighty-five patients were accrued; 174 provided useable pharmacokinetic data. Twenty-nine patients a parts per thousand yen60 years old (median 66; range 60-74) had a significantly higher BuCL versus those \u3c 60 years old (median 50; range 18-60): BuCL 236 versus 168 mL/min, p = 0.0002; BuCL/ABW 3.0 versus 2.1 mL/min/kg, p = 0.0001; BuCL/IBW 3.8 versus 2.6 mL/min/kg, p = 0.0035; BuCL/CBW 3.4 versus 2.6 mL/min/kg, p = 0.0005. Inter-patient variability in clearance (CV %) was up to 48 % in both age groups. Phenytoin administration, a potential confounder, did not affect BuCL, regardless of weight normalization (p \u3e 0.34). Contrary to our hypothesis, BuCL was significantly higher in older patients compared to younger patients in these studies and does not explain the previously reported increase in busulfan toxicity observed in older patients

Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry

Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 μCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0–2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities

Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST trial: A221701)

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher\u27s exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus