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Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.
Colorectal cancer (CRC) was diagnosed in approximately 143,000 individuals in the United States in 2007 (the most recent year US Cancer Statistics are available) and is the third most common cancer in men and women.1,2 CRC accounts for approximately 50,000 deaths each year and is largely preventable with recommended population screening.2,3 It is estimated that approximately 3% of CRCs are attributable to the hereditary condition Lynch syndrome (LS)–also referred to as hereditary nonpolyposis colorectal cancer.4-6 This autosomal dominant genetic disorder is associated with greatly increased risks for developing colorectal cancer and endometrial cancer.4-8 Standard population CRC screening guidelines fail to provide early detection or prevention for most LS colon cancers as they tend to occur at young ages.4-8 The diagnosis of LS is primarily based on the presence of a germline mutation in a mismatch repair (MMR) gene and applies to both individuals with and without a cancer diagnosis.7 Additional details regarding the clinical and genetic characteristics of this condition and testing strategies are provided in the "Background" section.
Prior clinical studies have demonstrated the feasibility and efficacy of screening all cases of newly diagnosed CRC for LS, a process which has been referred to as "universal screening."5,9-12 Furthermore, systematic evidence reviews have confirmed the analytic and clinical validity of available tumor screening tests to identify candidates for DNA analysis of the MMR genes associated with LS.7,8 These reviews also documented evidence of adequate test uptake among both individuals with CRC and their relatives, high levels of adherence to recommended surveillance, and minimal evidence of physical or psychological harms associated with testing or screening.6-8
Importantly, clinical research has found that of the 2.8% of subjects identified with LS by universal screening of all new CRCs, 50% were diagnosed over age 50 years, and 25% did not meet either the Amsterdam II diagnostic criteria13 or the revised Bethesda guidelines14 for LS.5 Thus, relying on age of diagnosis, family history, or tumor histology as defined by these criteria to determine who should undergo LS testing would miss a substantial number of affected individuals.15 Furthermore, clinical studies involving tumor screening of unselected endometrial cancers—the second most common malignancy associated with LS—have found a similar frequency (2.5%) of affected cases, many also not meeting age or family history criteria.16,17
In 2009, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) issued a recommendation regarding testing for LS in individuals with newly diagnosed CRC.6 The EWG is an independent, nonfederal panel involving multidisciplinary experts that uses a systematic evidence-based process for assessing the analytic validity, clinical validity, and clinical utility of genetic tests and other applications of genomic technology.18-20 Based on systematic reviews of the literature,7,8 the EWG determined that there is "sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer in order to reduce morbidity and mortality in their relatives."6 In addition, the EWG concluded that "there is moderate certainty that such a testing strategy would provide moderate population benefit."6 The EWG did not directly address implementation issues nor did they find sufficient evidence to recommend a specific testing strategy among the four examined. However, a subsequent analysis suggested that tumor immunohistochemistry (IHC) for the MMR gene-protein products, followed by testing of the tumor for the V600E mutation in the BRAF gene (BRAF testing), is the most cost-effective approach.10
Given the EWG recommendation and the evidence for potential population health benefits of screening for LS in all individuals with newly diagnosed CRC (hereafter referred to as universal LS screening), the following Department of Health and Human Services Healthy People objective was submitted in 2009 by the Centers for Disease Control and Prevention (CDC) Office of Public Health Genomics (OPHG) and adopted as a 2020 developmental objective: "Increase the proportion of persons with newly diagnosed colorectal cancer who receive genetic testing to identify Lynch syndrome."21 This objective is related to an overarching OPHG goal of reducing morbidity and mortality associated with LS in the United States through implementation of population-level genetic screening of new CRC cases and follow-up genetic testing of the relatives of patients with CRC found to carry a LS mutation (cascade testing).
To begin to construct the framework toward achieving this goal, OPHG convened a multidisciplinary meeting of clinical and public health experts, representing a variety of related specialties and organizations. The primary intent of this meeting was to explore possible approaches to population-level implementation of universal LS screening from the perspective of a public health/clinical partnership. Meeting participants included non-genetic physicians (gastroenterologists, surgeons, and family practitioners), genetics professionals (clinical geneticists, genetic counselors, and laboratory geneticists), epidemiologists and physicians from the CDC's Division of Cancer Prevention and Control and the National Cancer Institute, and state level public health genetics professionals. The participants were provided with several relevant publications before the meeting, including the EWG recommendation and associated evidence reviews.6-8
The meeting sought to address the context of the environment in which the EWG recommendation can be implemented, with consideration of existing clinical paradigms and standards of care. The specific meeting objectives were to consider:
This article provides background information relevant to understanding universal LS screening, summarizes the key discussion points of the meeting, and outlines multidisciplinary and multilevel strategies and approaches that were suggested to facilitate development of a population-level implementation protocol.
LS is primarily caused by dominantly inherited mutations in the DNA MMR genes MLH1, MSH2, MSH6, and PMS2. It is characterized by a substantially increased risk for CRC (lifetime risk: 54–74% males and 30–52% females) with a mean age of onset ranging from 42 to 61.7,8,22-26 Additionally, females with LS have a 28–60% lifetime risk for endometrial cancer.23-25 LS is also associated with modest increased risks (generally 10% by age 70 years) for other cancers, among them gastric, ovarian, small bowel, urinary tract, pancreatic, and sebaceous gland tumors.27,28 It should be noted that cancer risks and age of onset vary dependent on which gene is involved, with lower risks and later age of onset noted for individuals with MSH6 and PMS2 mutations.26,29 Intensive cancer surveillance, including early initiation and frequent follow-up with colonoscopy, has been shown to reduce CRC incidence and related mortality in individuals with LS.6,30-34 Furthermore, evidence supports the efficacy of risk-reducing hysterectomy and salpingoophorectomy, and guidelines suggest offering this surgery as an option for women with LS.35-37 Current CRC screening recommendations include colonoscopy every 1–2 years beginning at age 20–25 years.36-38 Annual transvaginal ultrasound of the uterus and ovaries and endometrial sampling are also recommended, although efficacy remains to be documented as does the utility of screening for other LS cancers.6,36-39
Preliminary screening for LS can be performed on paraffin-embedded CRC tumor tissue, before pursuing more costly and complicated germline DNA mutation analysis for diagnostic purposes. Two types of tumor screening for LS are available: microsatellite instability (MSI) testing and IHC. It is estimated that up to 90–95% of LS tumors will exhibit high MSI in contrast to 10–20% of sporadic CRCs.7,40,41 However, lower levels of sensitivity are noted with use of fewer microsatellite markers (80–84%) and when germline MSH6 mutations are involved (77%).7 IHC can be used to determine expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 in the tumor tissue, with an estimated sensitivity of 83% (95% confidence interval: 75–89%) reported.7 In general, absence of protein expression is suggestive of a germline mutation in the related LS gene, allowing for targeted DNA mutation analysis. Specificity for both MSI and IHC is close to 90%.7 However, additional tumor testing (BRAF) is suggested if loss of MLH1 expression is found on IHC, as this occurs in 75% of cases as a result of somatic promoter hypermethlyation.7,42,43 In addition, there are other less common genetic explanations for loss of MLH1 or MSH2 expression without evidence of an associated MMR germline mutation.44,45 Because of this, if no MMR mutation is found, additional genetic testing may be warranted if early age of onset, multiple primary tumors, or a strong family history is present.
Preliminary screening with MSI and IHC provides concordant results in >94% of cases, although each method has its advantages and disadvantages.7,46 When tumor screening results are positive, DNA sequencing and deletion/duplication analysis of the indicated MMR gene(s) can be pursued, which will identify more than 90% of LS disease-causing mutations. Once a LS mutation is identified, at-risk relatives can be tested for the specific mutation in the family relatively inexpensively and with essentially 100% accuracy—an approach known as cascade testing or family tracing. Because LS is an autosomal dominant disorder, on average 50% of first-degree relatives will also be affected. Therefore, it is highly advantageous to systematically identify and test biologic relatives of people with LS by following a mutation through a family, testing those at 50% risk, and then, if positive, testing their children and other at-risk family members before symptoms would typically begin to appear. Those who do not carry the familial mutation are generally considered at average risk for CRC and other LS cancers and can typically undergo CRC screening according to standard population guidelines. In contrast, individuals who are mutation positive require intensive surveillance, which typically involves colonoscopy every 1–2 years beginning at age 25 years, and screening for extracolonic cancers and the option of preventive surgery.36
If LS genetic screening was routinely performed on all cases of CRC in the United States, approximately 4,200 affected individuals would be identified each year (Figure 1). Assuming each individual identified with LS has four first-degree relatives with a 50% probability of inheriting the condition and eight second-degree relatives with a 25% probability, a total of 16,800 additional individuals with LS would be identified if all underwent evaluation for the familial mutation using a cascade testing approach. Based on conservative penetrance estimates, approximately half of these individuals (~8,400 cases) would develop CRC over the course of their lifetimes. Prospective studies of colonoscopic surveillance at 1–3-year intervals in individuals with LS have demonstrated a reduction in CRC incidence of 59–62%, indicating approximately 5,000 of these cancers would be prevented.31,32,47
Screening for LS on all newly diagnosed endometrial cancers (~42,000 new cases/year) would be expected to identify approximately 1,000 individuals with LS and 4,000 affected relatives, resulting in the potential to prevent an additional 1,500 CRC cases. Although LS screening of individuals with newly diagnosed endometrial cancer was not evaluated by the EWG, it is considered a logical next step based on available data and clinical application is already occurring.16
Although the aforementioned example is hypothetical and implies a best-case scenario, these figures illustrate that piloting implementation of universal LS screening on a population level is worth pursuing. This is supported by the EWG conclusion that benefits of testing for LS outweigh harms and the recent analysis which found universal LS screening to be highly cost-effective, even when more conservative uptake rates were applied.6,10
Several medical facilities across the country have existing protocols for routine LS genetic screening on newly diagnosed CRCs. Although no published statistics are available, a recent survey conducted on the National Society of Genetic Counselors cancer listserv reported that at least 30 centers/institutions are performing routine universal screening for LS, and several others are screening based on a specific criteria (e.g., age of diagnosis <50 years) (unpublished data). Some of these centers are also screening for LS on all or age subsets of newly diagnosed endometrial cancer cases. The protocols use various combinations of preliminary tumor testing (e.g., MSI only, IHC only, MSI and IHC, and IHC with BRAF) and differ with respect to consent and follow-up procedures.36 Systematic evaluation of these protocols and their effectiveness is needed to inform development of a population-level approach for universal LS screening, as existing data are limited. Notably, the one article published to date regarding clinical implementation of universal LS screening found lower uptake rates compared with those reported in research settings.48
It should be acknowledged that there have been arguments against the concept of universal LS screening. Hall49 contends that many aspects of the patient-level and social implications of adopting testing of all newly diagnosed CRC cases have not been adequately addressed. In addition to issues of access and cost associated with genetic counseling and testing, he noted the psychosocial burden to patients and families, limited societal benefit if there is poor uptake of testing and compliance with CRC screening, gaps in clinical resources and expertise, and the need to collect data regarding feasibility and effectiveness in real-world settings. Of these issues, lack of primary care provider knowledge and clinical expertise represents perhaps the most significant barriers to successful implementation of universal LS screening.
Peres11 interviewed clinicians from several institutions who noted difficulties with protocol logistics, concern that family history—already a challenge—would "fall by the wayside," and the experience that many patients would "rather not know," highlighting the need for at minimum, provision of information, and an "opt out" process rather than routine testing without patient knowledge. Ethical considerations regarding the level of consent required to perform LS screening on CRC tumors were recently addressed by Chubak et al.50 They suggested that although explicit informed consent should not be considered necessary for MSI testing, the issue is less certain for IHC testing given it can reveal specific genetic information regarding LS. They recommend further empirical study in this regard but emphasize that patients should be told results of both MSI and IHC screening, whether positive or negative.
In addition, there are issues regarding testing methodology which need to be addressed before a single universal LS screening protocol is promoted. For example, although preliminary tumor screening with IHC and BRAF has been suggested as the most cost-effective approach, this is likely related to improved specificity, rather than sensitivity. Furthermore, IHC scoring seems to show wide variability (kappa range: 0.49–0.79), suggesting that the diagnostic accuracy of current methods may be unacceptably low in some settings.51 Interpretation of the existing literature regarding the sensitivity and specificity of various tumor testing strategies is also confounded by incomplete testing of all four MMR genes and reports of ethnic variation.52 Further work is necessary to determine whether the limitations of IHC alone warrant performing both MSI and IHC or if these issues can be resolved by using centralized laboratories.
Finally, it is possible that the estimates of benefit in terms of reducing morbidity and mortality may not hold true for mutation- positive family members of LS cases detected through universal screening. Similar to the ascertainment bias which led to very high initial estimates of cancer risk in BRCA1/2 mutation carriers, the cancer penetrance and prevention rates typically quoted for LS are derived primarily from families identified due to multiple affected individuals and/or early age of onset.22,23,26,53 In addition, many studies have not included MSH6 and PMS2 mutation carriers, which are estimated to have lower penetrance and later age of onset for certain LS cancers compared with individuals with MLH1 or MSH2 mutations.26,29,54 The finding that many unselected CRC cases identified with LS do not fit classic diagnostic criteria raises the possibility that penetrance in these families may be lower and age of onset later, potentially resulting in a higher cost-benefit ratio if existing cancer screening protocols are applied. Hence, implementing universal LS screening should be accompanied by systematic collection of additional data to further assess clinical utility specifically in this context.
Following an introductory session and initial discussions, those meeting participants who had existing universal LS screening protocols or protocols in development shared their experiences, successes, and challenges, two of which are highlighted in this article. The Ohio State University (OSU) was one of the first centers to demonstrate the feasibility of screening all newly diagnosed CRC cases on both a research and a clinical basis, and their data provided part of the evidence for the EWG recommendation. The OSU current tumor testing protocol, which evolved from their previous research protocols, is illustrated in Figure 2. Importantly, they found that the addition of BRAF mutation analysis substantially reduced the IHC screen-positive rate (8–10% vs. 20%) (unpublished data, used with permission). However, uptake of counseling and testing among individuals with positive tumor screens has been much lower with clinical implementation than the high levels observed in their research studies, where follow-up counseling and testing were free and travel was not required.9,48 Of 34 individuals deemed appropriate for genetic consultation—out of 270 who underwent screening in the first 2 years of the clinical program—only seven completed the testing process.48
The clinical protocol followed by the Huntsman Cancer Institute is illustrated in Figure 3. To reduce the number of individuals who are "lost to follow up" and to improve testing uptake rates, their protocol automatically includes genetic counseling at the time of the postoperative appointment in patients whose tumor screens are positive. Their protocol currently excludes rectal cancers and colon cancers where surgery was not performed at their institute.
Multiple successes and challenges (both observed and potential) associated with the implementation of universal LS genetic screening and cascade testing of relatives were presented and discussed during the meeting. Table 1 provides a full list of these, whereas the most prominent themes which emerged in each category are highlighted below.
Although there have been some individual institutional successes in implementing universal LS screening, for a population benefit to be realized, a broader coordinated approach is needed. Exploring challenges and successes involved in state newborn screening programs and population-level carrier screening for single gene conditions such as sickle cell disease and Tay Sachs disease will provide valuable information in this regard. Central to these is the need to ensure adequate education and training of all involved. In particular, those at the policy level will need to be convinced that as with newborn screening, although only a small percentage of individuals are actually found to be affected, the impact of the diagnosis on health outcomes is profound, particularly as it applies to the multiple family members likely to be at risk for LS.
As with carrier and newborn screening programs, developing implementation protocols for universal LS screening will require significant collaborations between healthcare systems and public health agencies, with strategies and interventions targeted at multiple levels across the healthcare continuum. A framework for consideration of a multilevel approach is that of Taplin.55,56 This framework places the individual patient at the core, surrounded by concentric layers of key healthcare influences building on each other: family and social supports, the provider/healthcare team, the organization/practice setting, the local community environment, the state health policy environment, and the national health policy environment. Similarly, as outlined by Khoury,57 successful implementation and dissemination of evidence-based genomic medicine will require conscious consideration and integration of multiple components, including clinical and laboratory perspectives; behavioral, social, and communication factors; healthcare organizations; public health system perspectives; and policy, oversight, and regulatory frameworks.
To begin conceptualizing a multilayered approach toward universal LS screening on a population level, meeting participants considered the framework described earlier and worked in small groups to identify (1) the primary "layers" of importance; (2) who should be targeted in each layer—including what do they need and how do we reach them; (3) mechanisms to integrate the layers; and (4) ways to monitor uptake and outcomes of implementation. Both divergent and common themes were identified as part of this activity and are reviewed in the following paragraphs.
Considering an "outside-in" approach, one proposal was to convene national-level (e.g., National Institutes of Health) conferences to build consensus on (1) practical issues such as conveying test results to patients and family members; (2) development of standards and guidelines for pathology reports requiring inclusion of MSI/IHC results; (3) reviewing and revising practice recommendations through involvement of professional societies; and (4) identifying and addressing inadequacies in policy, facilities, and the workforce. State agencies could require LS test results to be included in tumor registries as a means of monitoring implementation. Genetic workforce issues could potentially be addressed at the state level by supporting a few regional genetic counselors to provide test follow-up. Buy in from payers is considered critical and could be spearheaded by the Centers for Medicare and Medicaid Services to cover not just the tumor screening, but follow-up genetic consultation, testing, and surveillance for individuals found to have LS and their at-risk family members. Involvement of hospital/medical group practices, primary care providers, and multiple provider specialties (e.g., pathology, gastroenterology, surgery, and genetics) will be essential to inform and support development of guidelines by national organizations, agencies, and professional societies.
Another focus was "multi-level education," ensuring entities at all layers—patients, family members, healthcare providers, public and private health systems, policy makers—are operating from the same understanding of the rationale for universal LS screening, the importance of genetic counseling and diagnostic testing for individuals whose tumor screens are positive, and the need to follow through with identification of at-risk family members and ensure appropriate surveillance of mutation-positive individuals. Public health entities can contribute on a state and national level by providing fact sheets and toll-free numbers for individuals and families, as well as centralized access to information for providers and payers. Professional guidelines, electronic medical record reminders, and clinical decision support tools could be used to enhance provider education and facilitate practice change. Providers will need access to an information technology infrastructure to facilitate this knowledge transfer, as they will be essential to educating individual patients and their family members. Creation of regionalized guidelines for healthcare systems, a national registry providing a network to connect families and providers, and ensuring compliance and quality assurance through tumor registries and central pathology groups were additional solutions offered to facilitate integration and monitoring. In particular, requiring LS tumor screening results to be included on all CRC pathology reports would allow for compliance to be monitored through the tumor registry system and provide an avenue to identify patients where appropriate follow-up needs to be confirmed. However, the time lapse between pathologic diagnosis and inclusion in the tumor registry and issues of patient confidentiality may limit what can be achieved through this method.
A third major approach concentrated on using the concepts and processes involved in newborn screening as a model for implementing universal LS screening on a population level. The original conceptualization of this idea is attributed to Heather Hampel and Albert de la Chapelle of the OSU (personal communication). National and/or state policy recommendations for universal LS screening would be needed, along with the creation of centralized state or regional laboratories. Individual pathology laboratories would be required to send a core of every CRC tumor specimen to the central laboratory, which would be set up to perform IHC on multiple samples simultaneously using tissue microarray technology. This should reduce cost and reading time per specimen and help to mitigate concerns regarding variability of IHC testing. A reliable reporting system would be essential, preferably by electronic medical record, as would the monitoring of appropriate follow-up. Results could be linked to state cancer registries as a check/balance to ensure the system is working. State level genetics professionals could be designated to facilitate follow-up counseling and testing of patients with positive tumor screens, particularly for systems where there is no easy access to genetic services. These professionals could network with their counterparts in other states to coordinate communication and follow-up with family members. Integration of the layers could be facilitated by providing incentives tied to outcomes both for the individual practitioners and for healthcare systems. These activities could also help improve understanding of CRC disparities in the US population.
Additional common themes and considerations emerged from the meeting discussions. It was recognized that pathologists and their related national organizations (e.g., the College of American Pathologists and the Association for Molecular Pathology) will be critical to the process of universal LS screening. Parallel to this will be the need for centralized/regional laboratories that will address issues of standardization of results and reporting, as well as quality control. Participants in general believed that the evidence is also compelling to consider universal genetic screening for LS in all cases of newly diagnosed endometrial cancer and that adding this and other Lynch-specific cancers (e.g., sebaceous gland tumors) once protocols are in place for CRC should be relatively straightforward.
It was acknowledged that recognizing and emphasizing the direct benefit to the patient with CRC diagnosed with LS will assist in addressing challenges associated with informed consent and insurance coverage. Although the EWG concluded at the time of their publication that insufficient evidence existed to alter treatment of LS-related CRCs, two systematic reviews have reported a potential adjuvant treatment impact of knowing the MSI status of CRC.58,59 Specifically, MSI-H colon cancers have shown a better prognosis and differential response to chemotherapy—particularly reduced efficacy of 5-fluorouracil.58,59 A recent retrospective cohort analysis also demonstrated a substantially lower risk for metachronous CRC in individuals with LS undergoing extensive versus segmental colon resection.60 In addition, the increased risk for developing second primary tumors (metachronous CRC and other cancers) will impact the screening and management of patients with CRC who are found to have LS. For example, standard practice after CRC diagnosis and treatment is to repeat colonoscopy at 1-year, then 3-year, and subsequently at 5-year intervals, assuming no abnormalities are noted.61 In contrast, ongoing colonoscopy every 1–2 years is standard of care for individuals with a LS-related CRC.6,36-38,62 Furthermore, screening with transvaginal ultrasound/endometrial biopsy and consideration of risk-reducing hysterectomy and oophorectomy are recommended for women with LS and a previous CRC.36-38,62
It was also noted that in accordance with the EWG recommendation, although family history should not be used to exclude individuals with newly diagnosed CRC from LS screening, it remains a valuable and important tool to identify unaffected individuals in the general population who may benefit from genetic evaluation for hereditary CRC. Thus, education of consumers and providers regarding the importance of family history and features suggestive of LS should continue to be encouraged. With increasing focus on the patient-centered medical home model, primary care providers will play an increasing role in identifying persons at high risk and referring patients for genetic counseling and predictive genetic testing.48 However, attempting to initiate a complementary and concurrent universal screening approach to identify healthy individuals at risk for LS based on family history was not considered feasible at this time.
The particular challenges of implementing universal LS genetic screening within the fragmented US healthcare system were discussed, including the need to enhance recognition of and avenues for addressing familial implications of the disease; dealing with the complexities of different insurance plans and limited avenues for reimbursement; and ensuring testing and surveillance of individuals identified with LS who may not have a primary care provider. Such issues as these may be most effectively addressed by public health entities partnering with those involved in clinical care, as well as with payers and policy makers. Using existing cancer registries and public health surveillance protocols could be one potential way to address some of these integration challenges.
Finally, it was recognized that working toward national implementation of screening for LS on all newly diagnosed CRC cases will require pilot studies and demonstration projects on a smaller scale, involving various types of healthcare systems and different state or regional platforms. Prospective data collection and comparative effectiveness research should be used to evaluate the benefits and limitations of implementing a newborn screening-like approach to universal LS screening in contrast to other potential or existing service delivery models. Further research on "real-world" clinical implementation is needed to collect additional data regarding uptake of genetic counseling and molecular testing of screen-positive patients, as well as the initiation of cascade testing and appropriate cancer surveillance in relatives of those individuals identified with LS. Such data will be critical to justify the cost and infrastructure requirements associated with initiating universal LS screening on a national level. It was further noted that in this era of limited resources, careful consideration of the appropriateness of using public health dollars toward population-level universal LS screening is warranted.
The following seven points summarize the key conclusions and recommendations that emerged from the meeting:
Despite the explosion over the past decade in the number and availability of genetic tests for a variety of human conditions and diseases, there have been no significant efforts on a national level to facilitate widespread genetic screening to prevent adult onset conditions in relatives of affected individuals using a public health model. In particular, although newborn screening protocols, which have existed in some form since the late 1960s, have continued to add rare genetic diseases to their panels, universal genetic screening for other health conditions at different life stages has not been attempted. LS in many respects may be the ideal genetic condition to launch this new era in public health genomics. This is because the condition—although rare in the general population—accounts for 2–3% of both CRC and endometrial cancers; relatively inexpensive and accurate preliminary screening of tumor tissue is available; sensitive and specific molecular genetic testing can facilitate identification of mutation-positive individuals and allow for cascade testing in relatives; identification of the mutation status of family members can reduce morbidity and mortality by initiating appropriate cancer screening for those at risk and avoiding unnecessary and costly screening of those who are mutation negative; and evidence exists of the potential impact of the diagnosis of LS on treatment, subsequent management, and surveillance for additional cancers in individuals with CRC.
At the same time, there are many questions which need to be answered before the EWG recommendation regarding universal LS screening can be implemented on a state, regional, or nationwide population level. Central to these issues is the need to educate consumers, providers, healthcare system administrators, payers, public health agencies, and state/federal policy makers regarding LS and its familial implications. There is a need for pilot population studies to gather more data, including but not limited to demonstration of the following: high levels of compliance with tumor tissue screening across multiple institutions; success of protocols designed to ensure accurate and timely reporting and follow-up of positive tumor results; reasonable levels of genetic counseling/testing uptake by patients with CRC with a positive tumor screen and family members of mutation-positive individuals; compliance with recommended cancer screening protocols and management; benefit to both the patient and family members; and minimal evidence of psychosocial and societal harm. Although many of the aforementioned issues have been demonstrated in high-risk clinic and research settings, clinical application on a wide-spread population level requires more study in these areas. These data will be essential to justify the expenditure on infrastructure that will be required to make population-level universal screening for LS a reality. It is only through multidisciplinary, multistakeholder involvement and cooperation—ideally facilitated though clinical/public health partnerships—that such accomplishments will be attainable.
Heather Hampel, MS, has received an honorarium from Myriad Genetic Laboratories, Inc. to serve on a Lynch syndrome Advisory Panel. The other authors declare no conflict of interest.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Cancer Institute.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Row Of Street Lamps At Misty Night Forming A Curve Stock PhotoBavaria,Electricity,Germany,Horizontal,Illuminated,In A Row,Large Group of Objects,Night,No People,Outdoors,Part of a Series,Photography,Repetition,Scale,Street LightPhotographer Raphael SchneiderCollection: Moment © 2007 Raphael SchneiderA row of street lamps on a bridge over the Danube near Deggendorf Germany. Shot at a misty winter night. The photo only shows the lamps focusing on showing the nice curve they are forming descending towards the bottom left corner.

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BSW Program Application
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text: Okay guys, I know that while Smogon is a large and effective community, we're not exactly the most tight-knit in the world. In think this because some people are estranged with one another and this may lead to the many cliques we have. I propose this thread be used for getting off our chests people we don't like and why, in order that we may understand and overcome our differences so that we may become one big effective unit. I'll start us off; - MoP is a nice guy, I can see that much, but I think his way of looking at things and saying his mind can offend others, sometimes if it's not meant to. - SDS could do with a chillax pill or two or ten. - locopoke needs to stop being stupid even where it doesn't matter - firecape too.


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Gagne, who will turn 33 this week, was acquired Tuesday from the defending champion Kings for a conditional draft pick. He took a red-eye, cross-country flight and appeared in his first game after being a healthy scratch for the past five with the Kings.
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Articles tagged work of art
8 Jul 2010 // 10:00 PM
Those Bravo executives are tricksters, fooling me into believing familiarity breeds contentment, not contempt. I'm totally hooked.READ more
//Mixed media
Blesst Chest "Blesst Chest Theme Song" (audio) (premiere) // Music
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Culture Belongs to the Alien in 'Spirits of Xanadu'
// Moving Pixels
"The symbols that the artifact in Spirits of Xanadu uses are esoteric -- at least for the average Western gamer. It is Chinese culture reflected back at us through the lens of alien understanding.READ the article


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Chemicals and Waste
GEF reception to celebrate start of INC7
King Hussein Bin Talal Convention Center
March 9
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DID YOU KNOW that many healthcare facilities cannot afford to dispose their waste properly?
Healthcare waste including used syringes can spread diseases, like Hep B, Hep C and HIV, to anyone who comes in contact with it and handles it improperly. Proper disposal of healthcare waste is costly and often healthcare facilities in developing countries don't have other options than to burn or bury it, releasing dangerous toxic into the environment.
DID YOU KNOW that human milk samples can be used to measure POPs exposure to the general population?
Mount Kenya, the second highest one of Africa, is one of the pilot sites to collect human milk samples, which then will be taken to laboratories for analysis. "If POPs (Persistent Organic Pollutants) even appear here, far away, from any industrial activities or overcrowded cities, it's an indication and confirmation of their global transportation", says Charles MIRIKAU who works at Department of Chemistry, University of Nairobi.


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just_another_bozo_on_this_bus 3 years, 5 months ago
"Merrick described the Legislative Research deficit projection as "static" and said it doesn't take into account economic growth that he believes tax cuts will prompt. He also said he believes more state spending could be cut."
If there is going to be economic growth in Kansas, it's going to happen as a result of national economic growth, and that growth is going to be hindered by austerity hysteria, not promoted by it. But he's right-- the Legislative Research deficit projection may be inaccurate because it's static-- it doesn't take into account that the economy will spiral downward because of austerity hysteria, and the deficit would then be much greater than $781.5 million within five years.
chootspa 3 years, 5 months ago
Wasn't there a model last year that did question how much growth it would take to make up for the lost revenue, and the answer was something astronomically high?
jafs 3 years, 5 months ago
I don't know about that, but you can figure it out logically.
Given tax rates, any cuts would have to generate multiple amounts of those cuts in growth to generate the same amount of revenue.
It's possible, but highly unlikely. Even Laffer doesn't claim tax cuts raise revenue, or even break even.
Hooligan_016 3 years, 5 months ago
This is just an absolute train wreck.
Richard Heckler 3 years, 5 months ago
"Republicans downplayed the deficit projection, although they also indicated Brownback's proposal would be altered"
MORE BS beyond belief. Brownback does not give a hoot for other republicans nor is he going to sign off on any alteration. His and ALEC's agenda is all that matters. If Brownback must exert executive privilege to get his way he will do so.
Brownback and ALEC have no use for republicans or democrats..... only their agenda.
DScully 3 years, 5 months ago
BS by the SB. If down the road he actually manages to eliminate the income tax, all hell will break loose!! Property taxes will go sky high, and that includes on renters, who have property taxes on the buildings they live in come out of their rent. Ergo, rents will soar. The SB is evil, no 2 ways about it!!!
bad_dog 3 years, 5 months ago
Ladies and gentlemen, next up on the Kansas legislative budgetary guillotine agenda: The Kansas Legislative Research Department. Surely private sector economists can do a better job with their projections and probably for less money, too. Perhaps there's someone in Wichita or Florida that can help...
DScully 3 years, 5 months ago
We need a good tornado to scoop him up and drop him where the sun don't shine....
Jean Robart 3 years, 5 months ago
I wish I had know how he would operate before the election. I never would have voted the way i did. I am so glad i am moving out of Kansas in another ten days.
Thinking_Out_Loud 3 years, 5 months ago
Well, that's fair. Yet last August and last November, I think it is fair to say the Governor's philosophy, approach, and agenda were clear. Knowing those things, Kansas voters still decisively gave legislative power to the conservative faction of the Republican party. In other words, Kansas is getting exactly the government it knowingly voted for.
Whether we will maintain the quality of life we have previously enjoyed, though, remains to be seen. Personally, I believe that we will not. I expect us to experience lower qualities of education, highway, consumer protection, and to experience more keenly than ever the social effects of poverty and poor public health. To support the policies we are implementing now we will have to dismantle the infrastructures needed to manage those services--meaning if we change our minds in five or six years, we will be unable to reverse what we have done, here.
Nonetheless, we have done it. Our only real option, now, is to roll up our shirtsleeves and work through our churches, synagogues, and social clubs with public service missions to pick up the pieces.
James Nelson 3 years, 5 months ago
Isn't it true that the number of church faithful is dropping? How is a shrinking number going to pick up an ever growing need like what the state is sloughing off?
Katara 3 years, 5 months ago
It is humorous to see someone with another state's name in their username tell people to leave Kansas.
Paul R Getto 3 years, 5 months ago
He is doing what he said he would, discounting the lies about protecting the poor and the schools.
Mike1949 3 years, 5 months ago
We allowed? I don't think so. The people tired of loosing their freedoms have been screaming about brownback ever since the corrupted republican party put him into office! I all have heard is if I don't like it, get out! (seriously) So much for democracy!
TongiJayhawk 3 years, 5 months ago
"the corrupted republican party put him into office! " I vaguely remember there was an election and he won by a wide margin. That is democracy! You have an election and someone wins. I'm not thrilled about Obama winning, but the people spoke and I'll deal with it! One of the great things about state rights is they don't have to completely follow the Federal Government.
just_another_bozo_on_this_bus 3 years, 5 months ago
The margin of his victory doesn't change the rules of math, or reverse the massive deficits that are coming down the pike.
James Nelson 3 years, 5 months ago
So, you admit you left Kansas because the republican party, who have governed Kansas forever, set the three taxes you mentioned unfairly high. It might take two or three years but if you decide to move back you won't believe how high property taxes will skyrocket if Sammy boy gets his wish on income taxes.
You must think also that the greedy, selfish, dictatorial ilk like the Koch brothers are the only hardworking, smart people around. I can only feel sorry for people like you with such thoughts.
JackMcKee 3 years, 5 months ago
The problem with your statement is that taxes aren't going down, they are shifting. If they do actually decrease it will come at the cost of education and social services. In that case, lookout Mississippi, we're gonna whip you in the race to the bottom.
dabbindan 3 years, 5 months ago
and now the portion/proportion the poor pay with income tax is higher, while the higher income portion has shrunk. when this was pointed out to sam he countered that the social services net would be enhanced to help with that. hmm. what do the low income earners need most to get out of the low income situation? certainly not less income and more social services. that's supposed to be the leftist trap isn't it?
pathetic man, that sam brownback. some of us could be motivated to leave the state out of embarrassment alone.
Paul R Getto 3 years, 5 months ago
Hope it's not as bad as I think that it's going to be .
I share your optimism but it will get much worse.
just_another_bozo_on_this_bus 3 years, 5 months ago
The Richest Pay Half The Effective Tax Rates Of The Poor In State And Local Taxes
January 30th, 2013 11:54 am Jason Sattler
"Trickle-down economics has trickled down to the states.
Virtually every state in the union takes a greater share of income from working families than the rich, according to a new report from the Institute on Taxation and Economic Policy (ITEP).
The report's stark conclusion finds that state and local tax rates are "fundamentally unfair," creating a hindrance to economic growth for the middle class that has been exacerbated by states moving away from progressive income taxes and toward consumption taxes.
"There's a good chance it's the so-called 'takers' who spend so much on necessities that they pay an effective tax rate of 10 or more percent, due largely to sales and property taxes," Matthew Gardner, executive director of ITEP and an author of the study, said.
Texas, which is often called the "low tax state," ranks among the states that have the highest taxes on the poor.
The bottom 20 percent pays 6 times the rate of the richest in Washington State, Florida, South Dakota, Illinois, Texas, Tennessee, Arizona, Pennsylvania, Indiana, and Alabama. ITEP called these states the "Terrible Ten" Most Regressive States.
Deductions and the practice of taxing capital gains at a lower rate make state tax codes more regressive. Policies like the earned income tax credit, which Michigan Republicans just cut, make the code more progressive, but only exist in 24 states and the District of Columbia.
Even where states do have progressive income tax rates, they're effectively shaped to put the burden on working families. "Alabama is a good example of a state with nominally graduated income tax rates that don't mean much in practice," the report states. "The state's top tax rate of 5 percent is not much lower than Louisiana's top rate — but the top rate kicks in at just $6,000 of taxable income for married couples. ""
RibMan 3 years, 5 months ago
The KS unemployment rate is approximately 5.5%. The national average is 7.9%.
Our economy is strong and positioned to become stronger.
States with no income tax (Florida, Texas, Tennessee, for example) tend to grow faster, create more jobs and have fewer people depending on government for their existence.
The gloom and doom comes from high tax States like California.
Facts are stubborn things. This is a debate worth having. Let's look at other States and study their experiences before declaring defeat. So far, it appears those States that move to lower income taxes do a better job of balancing their budgets and create more and better jobs. Which, of course, leads to a broader and deeper tax base.....which keeps governments operating.
George_Braziller 3 years, 5 months ago
Brownback needs to re-take Budgeting 101. When writing a budget you always over-estimate expenses, under-estimate revenue, and never include theoretical "maybe" money.
The organization where I used to work had a $1 million reserve but is now almost bankrupt because the ED wrote a deficit budget that ate up most of the reserve and made it balance by including revenue from a grant that not only hadn't been awarded, had not even been submitted. Within two years there were three rounds of layoffs, most of the services were been eliminated, and the staff has been cut by 75% from when I worked there.
Brownback is doing the same thing.
JayhawkFan1985 3 years, 5 months ago
Hallelujah, Merrick "believes" state spending can be further cut. It must be nice to have blind faith. I wonder how much time Merrick has spent at state agencies visiting with people who actually know how long the lines are, how many potholes there are, how many kids are in each classroom, etc. unfortunately for me, I have eyes, ears and a brain and know that. There is no meat left on the bone. Any further cuts will excise bone tissue.
The GOP is like the scarecrow...if they only had a brain...
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- S $8 BILLION WORTH OF AGENCIES AND PROGRAMS. June 29, 1998


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As one of the original 5+ million that purchased the Kindle Fire a new tablet love affair has transpired. I now own 3, one for each member of my family, and they're perfect to carry around for all our personal and business duties. The later being a huge unexpected surprise. Below are 10 sales and business applications that I recommend.
Category: Technology
What is Internet of Everything?
Your daily computer experience is most likely like mine. Normal email routine, some social media, and a couple of sites you visit. Truthfully for me it's starting to become a big yawn and I suspect for you as well. That's going to change in a big way with the Internet of Everything.
If you thought you're connected today, just wait. Imagine a world where it isn't just computers exchanging information, but everything. I'm talking about your auto, air conditioners, blood pressure cuffs, coffeemakers, business phones, televisions… everything! Enter Internet of things and Internet of Everything.
Business Cloud Communications, Social Media, and Web Presence.
Phones, phone lines, internet, websites, social media and the list goes on. Who would have thought that this new marketing – communications direction would be a company's newest and maybe even top concern?
So what's working and what isn't? Where do you put your time and money?
Mobile Presentation and Cloud Sales Tools.
Virtual sales presentations, or webinars, have become critical to today's sales success. We are a virtual cloud society after all. You need to be able to give a convincing virtual presentation that you can finalize online to be competitive. The potential client expects no less.
Technology Impact on Business.
Two of my favorite subjects are technology and business. It was, of course, destiny that an article on this subject would transpire. The idea began with a keynote presentation that I gave to a room full of CFO's and IT Directors. It just made sense to share with a larger audience.
Location Based Services Smart for Business
I recently investigated Foursquare, Yowza and others. I'm not a game guy and definitely don't use coupons but this mobile presence idea is intriguing to me and should be to you.
6 Hot Android Cloud Apps.
If you're looking for android cloud apps to make your Android OS device a powerful sales tool then look no further than these 6 business – sales solutions.


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Love it, hate it, good story, bad story... the media are going to keep reporting on ME/CFS no matter what. But isn't it time that we saw that coverage as an opportunity?
Discuss the article on the Forums.
Prednisolon and pituary MRI Imaging
Discussion in 'Hormones' started by Pearl, Mar 9, 2014.


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Paul Edward Haggis (born March 10, 1953) is a Canadian screenwriter, producer, and director. He is best known as screenwriter and producer for consecutive Best Picture Oscar winners, 2004's Million Dollar Baby and 2005's Crash, the latter of which he... also directed.
Connect any celebrity with Paul Haggis to see how closely they are linked... romantically!


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Growing up digital: How digital screens are changing the way we read
Jacquelyn Martin, Associated Press
This is the second in a three-part series that looks at the impact of new technlogy on kids and teens. Read part one: How digital culture is changing the way kids play. Read part three: How the Internet affects teen identity.
When Kevin Donahue got his daughter an iPad, she wasn't doing much of what he intended it for: Reading.
"All she was doing was playing Angry Birds," Donahue said.
At the same time, developer Suren Markosian had just quit his job with gaming company CrowdStar, giving him more time with his son Max. But Markosian found himself getting frustrated at story time.
"I couldn't really find any good books on the iPad. Kindle wasn't great for kids at all. There was no encouragement and you had to buy the books individually," Markosian said. "It was upsetting to me. So I decided to make it my personal mission to fix it."
So Donahue and Markosian teamed up to try and improve children's digital reading experience with their app, Epic!
Nicknamed "Netflix for e-books," Epic! is an app that allows children access to thousands of age-appropriate books, includes badges and encouragement for further reading and provides reports for parents about what and how long their kids are reading.
One of the main goals is to keep kids reading by minimizing device distraction, kind of like ensuring a book is so good it can be read without being distracted by the TV.
"We just want to encourage kids to read more," Markosian said. "We don't want to prevent kids from doing what they want to do. We want to make Epic! so great that they choose that over other things."
That's a relatively novel idea for technology that, while new, has rapidly taken up residence under toddlers' fingers. A Common Sense Media report published last year found that about as many children have their own tablet as adults did two years prior.
As a generation grows up glued to a screen, how will this change the way people read?
A recent study from the Kaiser Family Foundation found that American children ages 8-18 spend about 7 hours and 38 minutes with digital media daily. The study also found that with multitasking, kids were able to crunch almost 11 hours of content into that time if they were, say, listening to music or watching a movie on a digital device while crusing and web or doing homework.
Statistics like these should sound alarm bells for parents, says Jim Taylor, a psychologist and the author of "Raising Generation Tech: How to Prepare Your Children for a Media-Fueled World."
"Technology is neither good nor bad. It's how it's used," Taylor said. "The fundamentals of learning and thinking haven't changed. To learn something requires sustained focus. The inability to focus will limit or at least change their ability to engage in other, more complex forms of thinking."
The exception, not the rule
The main problem, Taylor says, is that too much exposure to this kind of media too early can spell trouble for developing kids.
"A child's brain is very malleable and they will adapt to whatever kind of stimulation they're exposed to," Taylor said. "If they're exposed to, for example, little bits of information, that's the way they will learn to predominantly process information. The problem there is that real learning takes time and focus to occur."
While there's evidence that reading on a screen vs. paper impacts comprehension, the research has been called into question.
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Rugged Ridge Replacement Passenger Side Door Mirror with LED Turn Signal, Black 11002.14
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MySQL 5 Stored Procedures: Relic or Revolution?
Stored procedures (or stored routines, to use the official MySQL terminology) are programs that are both stored and executed within the database server. Stored procedures have been features in closed-source relational databases, such as Oracle, since the early 1990s. However, MySQL added stored procedure support only in the recent 5.0 release and, consequently, applications built on the LAMP stack don't generally incorporate stored procedures. So, this is an opportune time to consider whether stored procedures should be incorporated into your MySQL applications.
Database stored programs first came to prominence in the late 1980s and early 1990s, during the client-server revolution. In the client-server applications of that time, stored programs had some obvious advantages:
Client-server applications typically had to balance processing load carefully between the client PC and the (relatively) more powerful server machine. Using stored programs was one way to reduce the load on the client, which might otherwise be overloaded.
Network bandwidth was often a serious constraint on client-server applications; execution of multiple server-side operations in a single stored program could reduce network traffic.
Maintaining correct versions of client software in a client-server environment was often problematic. Centralizing at least some of the processing on the server allowed a greater measure of control over core logic.
Stored programs offered clear security advantages because, in those days, application users typically connected directly to the database, rather than through a middle tier. As I discuss later in this article, stored procedures allow you to restrict the database account only to well-defined procedure calls, rather than allowing the account to execute any and all SQL statements.
With the emergence of three-tier architectures and Web applications, some of the incentives to use stored programs from within applications disappeared. Application clients are now often browser-based, security is predominantly handled by a middle tier, and the middle tier possesses the ability to encapsulate business logic. Most of the functions for which stored programs were used in client-server applications now can be implemented in middle-tier code (PHP, Java, C# and so on).
Nevertheless, many of the traditional advantages of stored procedures remain, so let's consider these advantages, and some disadvantages, in more depth.
Stored procedures are subject to most of the security restrictions that apply to other database objects: tables, indexes, views and so forth. Specific permissions are required before a user can create a stored program, and, similarly, specific permissions are needed in order to execute a program.
What sets the stored program security model apart from that of other database objects—and from other programming languages—is that stored programs may execute with the permissions of the user who created the stored procedure, rather than those of the user who is executing the stored procedure. This model allows users to perform actions via a stored procedure that they would not be authorized to perform using normal SQL.
This facility, sometimes called definer rights security, allows us to tighten our database security, because we can ensure that a user gains access to tables only via stored program code that restricts the types of operations that can be performed on those tables and that can implement various business and data integrity rules. For instance, by establishing a stored program as the only mechanism available for certain table inserts or updates, we can ensure that all of these operations are logged, and we can prevent any invalid data entry from making its way into the table.
In the event that this application account is compromised (for instance, if the password is cracked), attackers still will be able to execute only our stored programs, as opposed to being able to run any ad hoc SQL. Although such a situation constitutes a severe security breach, at least we are assured that attackers will be subject to the same checks and logging as normal application users. They also will be denied the opportunity to retrieve information about the underlying database schema (because the ability to run standard SQL will be granted to the procedure, not the user), which will hinder attempts to perform further malicious activities.
Another security advantage inherent in stored programs is their resistance to SQL injection attacks. An SQL injection attack can occur when a malicious user manages to "inject" SQL code into the SQL code being constructed by the application. Stored programs do not offer the only protection against SQL injection attacks, but applications that rely exclusively on stored programs to interact with the database are largely resistant to this type of attack (provided that those stored programs do not themselves build dynamic SQL strings without fully validating their inputs).
Excellent Article
Great article covering all points.
network traffic related issue
I also have the same question as Sachin, assuming store procedure perform at the same speed as a serial of raw sql code. If one (person or ORM) send all sql at once, it shouldn't make any difference right?
About network traffic using stored procedures and SQL statement
I have a confusion about the example you have given above. Suppose if i write a bunch of sql statements in my code and send them once over network. then the all statements will go to the server once. All the execution and condition checking will be done on the server and in the end i will get the status as the stored procedure will return. then can you tell me how will SP reduce network traffic??????
Also if i give an dll name that contain an SQL statement that load on server side. Then i think this does not increase network traffic.
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Practical Task Scheduling Deployment
July 20, 2016 12:00 pm CDT
One of the best things about the UNIX environment (aside from being stable and efficient) is the vast array of software tools available to help you do your job. Traditionally, a UNIX tool does only one thing, but does that one thing very well. For example, grep is very easy to use and can search vast amounts of data quickly. The find tool can find a particular file or files based on all kinds of criteria. It's pretty easy to string these tools together to build even more powerful tools, such as a tool that finds all of the .log files in the /home directory and searches each one for a particular entry. This erector-set mentality allows UNIX system administrators to seem to always have the right tool for the job.
Cron traditionally has been considered another such a tool for job scheduling, but is it enough? This webinar considers that very question. The first part builds on a previous Geek Guide, Beyond Cron, and briefly describes how to know when it might be time to consider upgrading your job scheduling infrastructure. The second part presents an actual planning and implementation framework.
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Children's and Kaul Pediatric Research Institute Release 2016 - 2017 Grant Application Guidelines
This year, once again, there are three categories of grants that will be funded: Established Investigator Awards, New Investigator Awards, and Quality/Safety/Educational Awards. All funded applications will be directed toward the improvement of child health care.
Established Investigator Awards: Up to two awards will be funded, one named in honor of Dr. Sergio Stagno and one named in memory of Dr. Rud Polhill, at an amount of $50,000 per year each for a maximum of two years.
New Investigator Awards: Up to five awards will be funded, at an amount of $30,000 per year each for a maximum of two years.
Quality/Safety/Educational Awards: Up to two Quality/Safety/Educational awards will be funded, at an amount of $10,000 each for one year.
Applications for all awards must be submitted electronically to firstname.lastname@example.com 4:30 p.m. on Friday, September 30, 2016. In addition - to ensure accuracy, completeness, and proper processing through UAB OSP – all Established and New Investigator grant applications should also be submitted to David Ingram on or before Wednesday, September 21st. Application guidelines and forms can also be found on the Pediatric Research Office (PRO) website at the following link:http://www.uab.edu/medicine/peds/research/funding. The PRO is available to assist all investigators with application development. Contact David Ingram or Cheryl Perry with any questions.
Dr. Tipple Selected as District Representative for Mid-Career Neonatology Group
DOP HSF Clinical Faculty Track (CFT) Promotion Committee Named
The Committee consists of seven members. Four at-large Associate Professors (3+ years in rank) and/or Professors are selected by the Pediatric HSF faculty. The Pediatric Vice Chair for Clinical Services, Children's of Alabama Chief Medical Officer, and Director of Pediatric Faculty Development serve as the three (3) appointed voting committee members. The seven members will elect a chair. At-Large members will serve a term of four years and may be reelected. Only one member of a division can be elected at any one time for the four at-large positions.
2016-2020 CFT Promotions Committee representatives are:
Cason Benton, M.D., at-large
Drew Davis, M.D., at-large
Jose Mestre, M.D., at-large
Annalise Sorrentino, M.D., at-large
Peter Glaeser, M.D., Pediatric Vice Chair for Clinical Services
Tony Fargason, M.D., Children's of Alabama Chief Medical Officer
Tina Simpson, M.D., Director of Pediatric Faculty Development
CFT Guidelines can be found on the DOP Faculty Promotion and Tenure website and can be accessed by clicking here.
NIH Awards UAB Three Maternal and Infant Health Grants
UAB is a member of the NICHD Maternal-Fetal Medicine Units Network, NICHD Neonatal Research Network, and the NICHD Global Network for Women's and Children's Health Research.
Over more than two decades, these networks have brought to UAB more than $20 million to fund research for pregnant women and babies, and the new awards total a $1.1 million base per year for the next five years.
For 25 years, UAB's Division of Neonatology has participated in the NICHD Neonatal Research Network (NRN) and was recently awarded $200,000 in base funds per year, with an additional $500,000 to $1 million per year to conduct additional research in the network.
The NRN was established in conjunction with the MFM Units Network to do similar research in neonatology. Areas addressed by the NRN include trials of therapies for sepsis, intraventricular hemorrhage, chronic lung disease and pulmonary hypertension, as well as the impact of drug exposure on child and family outcomes. Principal investigators for the network, Wally Carlo, M.D., Edwin M. Dixon Endowed Chair in Neonatology, and Namasivayam Ambalavananan, M.D., co-director of the Division of Neonatology, have led nationwide studies on ventilator care, antenatal steroids, chronic lung disease and neurodevelopmental outcomes.
A study in the NICHD NRN published in the NEJM reported that neonatal mortality has been decreased over the last 10 years, including decreases in almost all specific causes of neonatal mortality, because of improvements in care implemented in the NRN centers. A second paper showed that improvements in perinatal care, including obstetrical and neonatal interventions, are increasing survival rates substantially in the most premature babies. Survival rates are substantially increasing among those delivered at a gestational age of 20 weeks to 25 weeks and six days.
Click here to read the full press release on UAB News.
Letter from Mike Warren and Mitch Cohen about Medicaid
Azar's first step is the August 1 reduction of physician reimbursement by eliminating the Medicaid physician "payment bump," a move that could have significant adverse effects on children and Alabama's healthcare delivery system. The Alabama Medicaid agency has historically been one of the lowest state-funded agencies in the country.
A healthy, financially stable Medicaid program is vital to the more than 500,000 children served by the program, and it is critically important to the overall healthcare system in Alabama for all children. And it all begins with the primary care pediatricians and family medicine physicians in communities throughout Alabama who are on the front lines of healthcare.
Three-quarters of the Medicaid recipient population is under the age of 18 and account for almost half of the children in our State. For over 45 years, Medicaid has been an important part of Alabama's pediatric healthcare system. Importantly, Medicaid and commercial insurers provide coverage for 95 percent of our children. This is an outstanding achievement. As a result, the number of pediatricians across the State has increased, and Alabama ranks high in the nation in important child well-being markers, such as access to care, immunizations, timely preventive care and routine care for chronic illnesses. Our front line pediatricians and family care physicians do a great job but now that is all in jeopardy.
Approximately 60 percent of Children's of Alabama's patient population is Medicaid-eligible. Children's is the State's only comprehensive pediatric medical center and Medicaid is important to our ability to continue to provide care for all of the ill and injured children who come to us from each of Alabama's 67 counties every year. The children of Alabama desperately need for Medicaid to have stable, long-term funding that can help ensure medical care is accessible and available for all our children and for the next generation to come.
Children's of Alabama will continue to work with policy and legislative leaders to find long-term, sustainable funding for the State's Medicaid program. It is imperative that the pediatric healthcare framework not be disrupted and that we are well positioned to address the future needs of our children. The primary care physicians are at the epicenter of care for children in communities throughout Alabama. Their success and viability is simply good for kids.
The UAB Department of Pediatrics has provided, and continues to provide, training for pediatricians who are eager to provide care for the next generation of Alabama's children. A stable Medicaid program will help us retain these young doctors in our State, particularly in communities where the number of physicians is already low. Fewer community pediatricians will mean more local emergency room visits and increased costs.
Children's of Alabama, the UAB Department of Pediatrics and our healthcare partners across the State call on our governor, legislators and policymakers to do what is right for children and our medical community. Alabama must stop the annual, one-time band-aid approach to Medicaid funding. Alabama's children deserve a viable, sustainable long-term solution to Medicaid funding and only the governor and the legislature can do that job.
Mike Warren
President and CEO, Children's of Alabama
Mitch Cohen, M.D.
Children's Physician-in-Chief
Chair of the UAB Department of PediatricsChair of the UAB Department of Pediatrics
Dr. Kimberlin Receives $11.5 Million Contract to Look At Asymptomatic Congenital CMV and Neonatal HSV
The studies will assess treatment of babies born with congenital cytomegalovirus without symptoms, and frequency of neonatal herpes infections in the United States and Peru.
Almost one percent of babies born in the United States will have CMV, the largest non-genetic cause of sensory loss and mental disabilities. Ninety percent of these babies will be asymptomatic, or show no visible or laboratory evidence of the disease, at the time of birth. Early detection and close follow-up can lessen the effects of congenital CMV in infants. The new study, supported by a $10 million contract, will explore whether treating babies with four months of an oral drug – valganciclovir –that targets the virus can improve outcomes.
"UAB has been the world leader in studying congenital viral infections for the past 50 years," said David Kimberlin, M.D., who holds the Sergio Stagno, M.D., Endowed Chair in Pediatric Infectious Disease at UAB. "Our team of researchers and physicians have been instrumental in learning more about CMV and treating the disease. The next step is being able to identify and treat CMV in babies who are asymptomatic at birth."
A $1.5 million contract will support a study to assess the incidence of neonatal herpes infections in the United States and Peru using large databases in both countries to see how common the infection is. Knowledge gained from these investigations will inform future therapeutic studies aimed to decrease mother-to-infant transmission of herpes simplex virus. A prospective trial also will be conducted in Peru under this contract.
Other UAB researchers involved in these studies that improve the lives of children across the globe include Mary Wyatt Bowers, Penny Jester, Susan Branscum, Sara Davis, Juliette Southworth and Richard Whitley, M.D
Click here to read more on UAB News.


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Price: £13.09 inc. VAT (£10.91 ex. VAT)
Release Date: 02-06-09
Label: Indigo Sea Music
Catalog Number: ISMCD001
Barcode: 5065001460005
Musical Style: Meditation / Yoga / Mantra & Chants
This music produced by Rafael Szaban is designed to help create a suitable atmosphere for meditative practices, contemplation or altered state development and is based on the sacred OM mantra chant recorded live under the guidance of Swami Dharmanada Saraswati Maharaj.
The CD has been used by Reiki healers and is also a favourite amongst students and teachers at the Arthur Findlay College of Psychic Studies.
The mantra is chanted by almost 30 people. Other instruments include: flute, tambura, chimes, bells, sampled Chinese guitar, prepared bells, sampled harp.
There are two tracks each lasting about 36 minutes. Both tracks are divided into two parts. Part one is melodic, part two is more calm and creates a peaceful and stilling effect. The CD can be played as one continuous piece with only a short break between track one and two.
The 'Be Still' CD was released in 2003 and was the first release on the Indigo Sea Music label.
|Be Still - Part One
|Be Still - Part Two
|The Great Peace - Part One
|The Great Peace - Part Two
Copyright © 1996-2016 DiscorD Distribution. All rights reserved. E&OE. Written terms available on request


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Open house schedules throughout Chicagoland are lighter than might be expected this Sunday, perhaps due to the Bears - Seahawks game. If TV viewers shun the game, as ticket buyers seem to be doing, open house attendance might by higher than expected.
Only four Sunday open houses are scheduled in Lake Forest bear country, as of Wednesday morning, at prices ranging from $299,000 to $1,200,000. All four of the homes are open from 1 to 3.
At the low end of the range are 2,000 square foot 2- and 3- bedroom, 2-bath condos at 1260 and 1350 N Western Ave, priced at $319K and $299K, respectively.
The renovated 5-bedroom, 3-bath bungalow (pictured above) at 140 Summit Pl near downtown Lake Forest is offered at $689,000.
The Bears game will be viewable on the flat-screen TV at the 5-bedroom, 4 ½ bath 1980s-vintage home at 1341 Estate Ln in southwest Lake Forest. According to the listing it's a "forever home" overlooking the original Lasker Estate.
Filed under: Uncategorized
Tags: Lake Forest, Open house, real estate, single-family


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and THERE is a gap left in spyders around 102 SO yes IT IS POSSIBLEactually i think we'll do itbut sometime in 2010 not 2009I BELIEVE THE CHART IS SETTING up for a very hard sharp correction soon and then we WILL get a higher low TO GO TO A HIGHER HIGH.just what i thinki don't think spx goes to my 417 target till 2011 or 2013but ultimately it's still going to 1994 levels atleast IMHOso this year i'm looking for spyders back into 70'sthen a steady slow up market all the way into mid term elections.lets c BUT i tell u what when spyders do get in 70's i'm not gonna be the first one to try and catch the fall. HELL NOlol


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Bachelder Gloria MD - Kenai, AK - Phone: (907) 283-9118
Dena'ina Health Clinic - Kenai, AK - Phone: (907) 335-2100
Hahn Kenneth S MD - Kenai, AK - Phone: (907) 283-6030
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Peninsula Insta Care - Kenai, AK - Phone: (907) 283-5977
'Arthritis Specialists' are medical professionals who are responsible for providing treatment to patients affected with arthritis. There are many forms of arthritis, the common being osteoarthritis and rheumatoid arthritis in Kenai. For treating them, clinical tests like blood tests, radiology,etc, are done and after the detection, arthritis specialists give the necessary treatment for their recovery. In Kenai, the treatment differs according to the type of arthritis detected and arthritis specialists treat them accordingly.
At the beginning of medication, the arthritis specialists in Kenai give medicines having less power and increase as and when required. In Kenai, both physical as well as occupational therapy is given by the arthritis specialist for relieving the patients from the excruciating pain of arthritis.
Alliance for Green Heat and NYSERDA Announce Seven Finalists in International Pellet Stove Competition
Two New York teams are among the finalists (Long Island, NY) Alliance for Green Heat and the New York State Energy Research and Development Authority (NYSERDA) today announced that seven pellet stoves have been chosen as finalists in the Pellet Stove Design Challenge. This international competition, administered by the Alliance for Green Heat, identifies innovative low emissions and high efficiency..


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Vox Logo T-ShirtProduct #411700 Vox 411700 OHAAB Short Sleeve Mens T-Shirts https://www.esnapw.com/rses/ESnapServlet?MerchantNumberSent=63655
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I am an enrolled member of a Tribe that is denying my husband to live with me in my owned home on the Reservation. He has not committed any crimes on Federal Land but it has gone personal. All that was requested is a letter from the Tribe to allow his Probation Officer to come to my home once a month. They have stated they take care of their own. Other Felons live on the Rez. (murderers, drug traffickers, sex offenders who are Indians.) Need your opinions.
Native American Law Attorney
If the Tribe is enforcing the exclusion of your husband from reservation boundaries, you may be able to seek a writ of habeas corpus in federal court under the Indian Civil Rights Act for violation of due process. You may be able to also seek relief in tribal court or before the tribal council.
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