Hypofractionated radiotherapy has the potential for second cancer reduction

<p>Abstract</p> <p>Background and Purpose</p> <p>A model for carcinoma and sarcoma induction was used to study the dependence of carcinogenesis after radiotherapy on fractionation.</p> <p>Materials and methods</p> <p>A cancer induction model for radiotherapy doses including fractionation was used to model carcinoma and sarcoma induction after a radiation treatment. For different fractionation schemes the dose response relationships were obtained. Tumor induction was studied as a function of dose per fraction.</p> <p>Results</p> <p>If it is assumed that the tumor is treated up to the same biologically equivalent dose it was found that large dose fractions could decrease second cancer induction. The risk decreases approximately linear with increasing fraction size and is more pronounced for sarcoma induction. Carcinoma induction decreases by around 10% per 1 Gy increase in fraction dose. Sarcoma risk is decreased by about 15% per 1 Gy increase in fractionation. It is also found that tissue which is irradiated using large dose fractions to dose levels lower than 10% of the target dose potentially develop less sarcomas when compared to tissues irradiated to all dose levels. This is not observed for carcinoma induction.</p> <p>Conclusions</p> <p>It was found that carcinoma as well as sarcoma risk decreases with increasing fractionation dose. The reduction of sarcoma risk is even more pronounced than carcinoma risk. Hypofractionation is potentially beneficial with regard to second cancer induction.</p

Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia

Although KIT mutations are present in 20–25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications

Genetic risk variants associated with in situ breast cancer

INTRODUCTION: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS. METHODS: To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile. RESULTS: We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons &lt;0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies. CONCLUSIONS: Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus

Whose Sense of Place? A Political Ecology of Amenity Development

Using a political ecology framework, this chapter examines the ways in which sense of place and amenity migration contribute to alternative residential development, which relies on uneven use of conservation subdivision features in the American West. Using case studies from Central Oregon, this chapter demonstrates how senses of place and developer decision-making are tied to wider political economic changes. It highlights the roles that amenity migrants and developers, two groups that are sometimes identical, play in landscape transformations that simultaneously draw on a particular sense of place and commodify landscapes in new ways

An Estimate of Avian Mortality at Communication Towers in the United States and Canada

Avian mortality at communication towers in the continental United States and Canada is an issue of pressing conservation concern. Previous estimates of this mortality have been based on limited data and have not included Canada. We compiled a database of communication towers in the continental United States and Canada and estimated avian mortality by tower with a regression relating avian mortality to tower height. This equation was derived from 38 tower studies for which mortality data were available and corrected for sampling effort, search efficiency, and scavenging where appropriate. Although most studies document mortality at guyed towers with steady-burning lights, we accounted for lower mortality at towers without guy wires or steady-burning lights by adjusting estimates based on published studies. The resulting estimate of mortality at towers is 6.8 million birds per year in the United States and Canada. Bootstrapped subsampling indicated that the regression was robust to the choice of studies included and a comparison of multiple regression models showed that incorporating sampling, scavenging, and search efficiency adjustments improved model fit. Estimating total avian mortality is only a first step in developing an assessment of the biological significance of mortality at communication towers for individual species or groups of species. Nevertheless, our estimate can be used to evaluate this source of mortality, develop subsequent per-species mortality estimates, and motivate policy action

Posttraumatic stress disorder among female street-based sex workers in the greater Sydney area, Australia

BACKGROUND: This paper examines rates of exposure to work-related violence and other trauma, and the prevalence of lifetime and current posttraumatic stress disorder (PTSD) among female street-based sex workers. It also investigates associations between current PTSD symptoms and: demographic characteristics, psychiatric comorbidity, injecting and sex risk behaviours, and trauma history. METHODS: Cross sectional data collected from 72 women via face to face structured interviews. The interview included structured diagnostic assessment of DSM-IV PTSD; drug dependence; depression; experience of childhood trauma; and an assessment of sex working history. RESULTS: All but one of the women interviewed reported experiencing trauma, with the majority reporting multiple traumas that typically began in early childhood. Child sexual abuse, adult sexual assault and work related violence were commonly reported. Just under half of the women met DSM-IV criteria for PTSD and approximately one-third reported current PTSD symptoms. Adult sexual assault was associated with current PTSD symptoms. Depression and drug dependence were also highly prevalent; cocaine dependence in particular was associated with elevated rates of injecting risk and sexual risk behaviours. CONCLUSION: These women reported complex trauma histories and despite ongoing opportunities for clinical intervention, they continued to experience problems, suggesting that current models of treatment may not be appropriate. More targeted interventions, and integrated mental health and drug treatment services are needed to address the problems these women are experiencing. Outreach services to these women remain a priority. Education strategies to reduce risky injecting and sexual behaviours among sex workers should also remain a priority

Can working with the private for-profit sector improve utilization of quality health services by the poor? A systematic review of the literature

BACKGROUND: There has been a growing interest in the role of the private for-profit sector in health service provision in low- and middle-income countries. The private sector represents an important source of care for all socioeconomic groups, including the poorest and substantial concerns have been raised about the quality of care it provides. Interventions have been developed to address these technical failures and simultaneously take advantage of the potential for involving private providers to achieve public health goals. Limited information is available on the extent to which these interventions have successfully expanded access to quality health services for poor and disadvantaged populations. This paper addresses this knowledge gap by presenting the results of a systematic literature review on the effectiveness of working with private for-profit providers to reach the poor. METHODS: The search topic of the systematic literature review was the effectiveness of interventions working with the private for-profit sector to improve utilization of quality health services by the poor. Interventions included social marketing, use of vouchers, pre-packaging of drugs, franchising, training, regulation, accreditation and contracting-out. The search for published literature used a series of electronic databases including PubMed, Popline, HMIC and CabHealth Global Health. The search for grey and unpublished literature used documents available on the World Wide Web. We focused on studies which evaluated the impact of interventions on utilization and/or quality of services and which provided information on the socioeconomic status of the beneficiary populations. RESULTS: A total of 2483 references were retrieved, of which 52 qualified as impact evaluations. Data were available on the average socioeconomic status of recipient communities for 5 interventions, and on the distribution of benefits across socioeconomic groups for 5 interventions. CONCLUSION: Few studies provided evidence on the impact of private sector interventions on quality and/or utilization of care by the poor. It was, however, evident that many interventions have worked successfully in poor communities and positive equity impacts can be inferred from interventions that work with types of providers predominantly used by poor people. Better evidence of the equity impact of interventions working with the private sector is needed for more robust conclusions to be drawn

Range Expansion Drives Dispersal Evolution In An Equatorial Three-Species Symbiosis

A-09-14International audienceBackground Recurrent climatic oscillations have produced dramatic changes in species distributions. This process has been proposed to be a major evolutionary force, shaping many life history traits of species, and to govern global patterns of biodiversity at different scales. During range expansions selection may favor the evolution of higher dispersal, and symbiotic interactions may be affected. It has been argued that a weakness of climate fluctuation-driven range dynamics at equatorial latitudes has facilitated the persistence there of more specialized species and interactions. However, how much the biology and ecology of species is changed by range dynamics has seldom been investigated, particularly in equatorial regions. Methodology/Principal Findings We studied a three-species symbiosis endemic to coastal equatorial rainforests in Cameroon, where the impact of range dynamics is supposed to be limited, comprised of two species-specific obligate mutualists –an ant-plant and its protective ant– and a species-specific ant parasite of this mutualism. We combined analyses of within-species genetic diversity and of phenotypic variation in a transect at the southern range limit of this ant-plant system. All three species present congruent genetic signatures of recent gradual southward expansion, a result compatible with available regional paleoclimatic data. As predicted, this expansion has been accompanied by the evolution of more dispersive traits in the two ant species. In contrast, we detected no evidence of change in lifetime reproductive strategy in the tree, nor in its investment in food resources provided to its symbiotic ants. Conclusions/Significance Despite the decreasing investment in protective workers and the increasing investment in dispersing females by both the mutualistic and the parasitic ant species, there was no evidence of destabilization of the symbiosis at the colonization front. To our knowledge, we provide here the first evidence at equatorial latitudes that biological traits associated with dispersal are affected by the range expansion dynamics of a set of interacting species