Deletion Mutations in an Australian Series of HNPCC Patients

Hereditary non polyposis colorectal cancer (HNPCC) is characterized by the presence of early onset colorectal cancer and other epithelial malignancies. The genetic basis of HNPCC is a deficiency in DNA mismatch repair, which manifests itself as DNA microsatellite instability in tumours. There are four genes involved in DNA mismatch repair that have been linked to HNPCC; these include hMSH2, hMLH1, hMSH6 and hPMS2. Of these four genes hMLH1 and hMSH2 account for the majority of families diagnosed with the disease. Notwithstanding, up to 40 percent of families do not appear to harbour a change in either hMSH2 or hMLH1 that can be detected using standard screening procedures such as direct DNA sequencing or a variety of methods all based on a heteroduplex analysis

Frequency of the Common MYH Mutations (G382D and Y165C) in MMR Mutation Positive and Negative HNPCC Patients

Recently mutations in the MYH gene have been associated with a milder form of adenomatous polyposis which is characterized by a variable level of colonic polyps ranging from a few to several hundred. In the context of HNPCC it is not unusual to identify patients with a smattering of polyps. The MYH gene product is involved in DNA repair and indeed the hMSH2/hMSH6 complex (both genes being essential elements of the DNA mismatch repair pathway) is required to stimulate MYH activity. We reasoned that because of the clinical similarity of a subset of HNPCC patients to those described with MYH mutations and the role of the hMSH2/hMSH6 complex in the activation of MYH protein that MYH mutations may account for a small proportion of HNPCC patients. In a study of 442 HNPCC patients we identified MYH mutations at the same frequency as that expected in the general population. Nevertheless, two HNPCC families were identified harbouring biallelic changes in MYH

Awareness and implementation of tobacco dependence treatment guidelines in Arizona: Healthcare Systems Survey 2000

<p>Abstract</p> <p>Background</p> <p>This paper presents findings from the Tobacco Control in Arizona Healthcare Systems Survey, conducted in 2000. The purpose of the survey was to assess the status of Arizona healthcare systems' awareness and implementation of tobacco cessation and prevention measures.</p> <p>Methods</p> <p>The 20-item survey was developed by The University of Arizona HealthCare Partnership in collaboration with the Arizona Department of Health Services Bureau of Tobacco Education and Prevention. It was mailed to representatives of Arizona's 40 healthcare systems, including commercial and Medicare managed care organizations, "managed Medicaid" organizations, Veterans Affairs Health Care Systems, and Indian Health Service Medical Centers. Thirty-three healthcare systems (83%) completed the survey.</p> <p>Results</p> <p>The majority of healthcare systems reported awareness of at least one tobacco cessation and prevention clinical practice guideline, but only one third reported full guideline implementation. While a majority covered some form of behavioral therapy, less than half reported covering tobacco treatment medications. "Managed Medicaid" organizations administered through the Arizona Health Care Cost Containment System were significantly less likely to offer coverage for behavioral therapy and less likely to cover pharmacotherapy than were their non-Medicaid counterparts in managed care, Veterans Affairs Health Care Systems and Indian Health Service Medical Centers.</p> <p>Conclusion</p> <p>Arizona healthcare system coverage for tobacco cessation in the year 2000 was comparable to national survey findings of the same year. The findings that only 10% of "Managed Medicaid" organizations covered tobacco treatment medication and were significantly less likely to cover behavioral therapy were important given the nearly double smoking prevalence among Medicaid patients. Throughout the years of the program, the strategic plan of the Arizona Department of Health Services Bureau of Tobacco Education and Prevention has included the goal of identifying and eliminating tobacco related disparities for special populations, including low-income groups. Of importance, in 2008 the Arizona Health Care Cost Containment System was authorized to provide tobacco cessation pharmacotherapy as a covered benefit for its members.</p

Activation of optimally and unfavourably oriented faults in a uniform local stress field during the 2011 Prague, Oklahoma, sequence

The orientations of faults activated relative to the local principal stress directions can provide insights into the role of pore pressure changes in induced earthquake sequences. Here, we examine the 2011 M 5.7 Prague earthquake sequence that was induced by nearby wastewater disposal. We estimate the local principal compressive stress direction near the rupture as inferred from shear wave splitting measurements at spatial resolutions as small as 750 m. We find that the dominant azimuth observed is parallel to previous estimates of the regional compressive stress with some secondary azimuths oriented subparallel to the strike of the major fault structures. From an extended catalogue, we map ten distinct fault segments activated during the sequence that exhibit a wide array of orientations. We assess whether the five near-vertical fault planes are optimally oriented to fail in the determined stress field. We find that only two of the fault planes, including the M   5.7 main shock fault, are optimally oriented. Both the M 4.8 foreshock and M   4.8 aftershock occur on fault planes that deviate 20–29° from the optimal orientation for slip. Our results confirm that induced event sequences can occur on faults not optimally oriented for failure in the local stress field. The results suggest elevated pore fluid pressures likely induced failure along several of the faults activated in the 2011 Prague sequence

Impact of Feeding Aspergillus Subspecies Blend and Di! erent Corn Processing Methods on Finishing Beef Cattle Performance and Carcass Characteristics

A feedlot study utilizing 320 crossbred calf- fed steers (initial body weight 588 lb) compared the effect of feeding an Aspergillus additive in either dry- rolled corn or high- moisture corn finishing diets on cattle performance and carcass characteristics. Steers were fed 0 g/steer daily or 10 g/steer daily Aspergillus for both corn processing methods. # ere were no significant interactions between corn processing method and Aspergillus. Feeding finishing cattle Aspergillus did not impact performance compared to feeding none. Cattle fed dry- rolled corn had greater final body weight, dry matter intake, and gain compared to high- moisture corn diets. But cattle fed high- moisture corn had a 6.25% decrease in feed- to- gain compared to dry- rolled corn. These data suggest that feeding Aspergillus does not affect performance. The lower dry matter intake and average daily gain observed would suggest a potential acidosis problem for high- moisture corn compared to dry- rolled corn- based finishing diets

The Association of the COMT V158M Polymorphism with Endometrial/Ovarian Cancer in HNPCC Families Adhering to the Amsterdam Criteria

Catechol-O-methyltransferase (COMT) is vital for the conjugation of catechol estrogens that are produced during oestrogen metabolism. The efficiency of this process varies due to a polymorphism in COMT, which changes valine to methionine (V158M). The Met genotypes slow the metabolism of catechol oestrogens, which are agents that are capable of causing DNA damage through the formation of DNA adducts and reactive oxygen species (ROS) production. The slower metabolism of catechol oestrogens results in there being a higher circulating concentration of these oeastrogens and consequently greater probability of DNA damage. To determine whether metabolic inefficiencies of oeastrogen metabolism are associated with the development of malignancy in hereditary non-polyposis colorectal cancer (HNPCC), we studied the V158M polymorphism in COMT in a large cohort of 498 HNPCC patients from Australia and Poland that were either mutation positive (n = 331) or negative (n = 167) for mismatch repair (MMR) gene mutations (hMLH1 or hMSH2). HNPCC is a familial predisposition to colorectal cancer (CRC) and extracolonic cancers that include endometrial cancer

Progress Towards a Multi-Modal Capsule Endoscopy Device Featuring Microultrasound Imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1. μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with single-photon avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials has been examined as a function of frequency and ultrasound transducers have been developed to operate at centre frequencies in the range 15 - 50 MHz. Ex vivo testing of porcine tissue has been performed, generating images of interest to the clinical community, demonstrating the viability of the Sonopill concept

Effect of Corn Residue Harvest Method on In Vivo and In Vitro Digestibility

A digestion study was conducted using 18 crossbred wether lambs to evaluate the effects of corn residue harvesting method and ensiling on the digestibility of corn residue. Husks had the greatest digestibility compared to any of the harvesting methods. No differences were observed for the digestibility of husklage, ensiled husklage, or stalklage. None of the harvest methods resulted in residue digestibilities similar to husks