Classes of Multiple Decision Functions Strongly Controlling FWER and FDR

This paper provides two general classes of multiple decision functions where each member of the first class strongly controls the family-wise error rate (FWER), while each member of the second class strongly controls the false discovery rate (FDR). These classes offer the possibility that an optimal multiple decision function with respect to a pre-specified criterion, such as the missed discovery rate (MDR), could be found within these classes. Such multiple decision functions can be utilized in multiple testing, specifically, but not limited to, the analysis of high-dimensional microarray data sets.Comment: 19 page

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

Opuntia in México: Identifying Priority Areas for Conserving Biodiversity in a Multi-Use Landscape

BACKGROUND: México is one of the world's centers of species diversity (richness) for Opuntia cacti. Yet, in spite of their economic and ecological importance, Opuntia species remain poorly studied and protected in México. Many of the species are sparsely but widely distributed across the landscape and are subject to a variety of human uses, so devising implementable conservation plans for them presents formidable difficulties. Multi-criteria analysis can be used to design a spatially coherent conservation area network while permitting sustainable human usage. METHODS AND FINDINGS: Species distribution models were created for 60 Opuntia species using MaxEnt. Targets of representation within conservation area networks were assigned at 100% for the geographically rarest species and 10% for the most common ones. Three different conservation plans were developed to represent the species within these networks using total area, shape, and connectivity as relevant criteria. Multi-criteria analysis and a metaheuristic adaptive tabu search algorithm were used to search for optimal solutions. The plans were built on the existing protected areas of México and prioritized additional areas for management for the persistence of Opuntia species. All plans required around one-third of México's total area to be prioritized for attention for Opuntia conservation, underscoring the implausibility of Opuntia conservation through traditional land reservation. Tabu search turned out to be both computationally tractable and easily implementable for search problems of this kind. CONCLUSIONS: Opuntia conservation in México require the management of large areas of land for multiple uses. The multi-criteria analyses identified priority areas and organized them in large contiguous blocks that can be effectively managed. A high level of connectivity was established among the prioritized areas resulting in the enhancement of possible modes of plant dispersal as well as only a small number of blocks that would be recommended for conservation management

Group Decisions in Biodiversity Conservation: Implications from Game Theory

. This paper shows how game theory may be used to inform group decisions in biodiversity conservation scenarios by modeling conflicts between stakeholders to identify Pareto–inefficient Nash equilibria. These are cases in which each agent pursuing individual self–interest leads to a worse outcome for all, relative to other feasible outcomes. Three case studies from biodiversity conservation contexts showing this feature are modeled to demonstrate how game–theoretical representation can inform group decision-making.–agent fish and coral conservation scenario from the Philippines. In each case there is reason to believe that traditional mechanism–design solutions that appeal to material incentives may be inadequate, and the game–theoretical analysis recommends a resumption of further deliberation between agents and the initiation of trust—and confidence—building measures. that formal mechanism–design solutions may backfire in certain cases. Such scenarios demand a return to group deliberation and the creation of reciprocal relationships of trust

Chagas Disease Risk in Texas

Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and human population data at the county level. We modeled the distribution of each vector species using occurrence data from México and the United States and environmental variables. We then computed the ecological risk from the distribution models and combined it with disease incidence data to produce a composite risk map which was subsequently used to calculate the populations expected to be at risk for the disease. South Texas had the highest relative risk. We recommend mandatory reporting of Chagas disease in Texas, testing of blood donations in high risk counties, human and canine testing for Chagas disease antibodies in high risk counties, and that a joint initiative be developed between the United States and México to combat Chagas disease

Loss of Let-7 Up-Regulates EZH2 in Prostate Cancer Consistent with the Acquisition of Cancer Stem Cell Signatures That Are Attenuated by BR-DIM

The emergence of castrate-resistant prostate cancer (CRPC) contributes to the high mortality of patients diagnosed with prostate cancer (PCa), which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs). Recent studies have shown that deregulated expression of microRNAs (miRNAs) contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2), a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3′UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3′-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM) up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact

Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from north India

BACKGROUND: Literature on the spectrum of opportunistic disease in human immunodeficiency virus (HIV)-infected patients from developing countries is sparse. The objective of this study was to document the spectrum and determine the frequency of various opportunistic infections (OIs) and non-infectious opportunistic diseases, in hospitalised HIV-infected patients from north India. METHODS: One hundred and thirty five consecutive, HIV-infected patients (age 34 ± 10 years, females 17%) admitted to a tertiary care hospital in north India, for the evaluation and management of an OI or HIV-related disorder between January 2000 and July 2003, were studied. RESULTS: Fever (71%) and weight loss (65%) were the commonest presenting symptoms. Heterosexual transmission was the commonest mode of HIV-acquisition. Tuberculosis (TB) was the commonest OI (71%) followed by candidiasis (39.3%), Pneumocystis jiroveci pneumonia (PCP) (7.4%), cryptococcal meningitis and cerebral toxoplasmosis (3.7% each). Most of the cases of TB were disseminated (64%). Apart from other well-recognised OIs, two patients had visceral leishmaniasis. Two cases of HIV-associated lymphoma were encountered. CD4+ cell counts were done in 109 patients. Majority of the patients (82.6%) had CD4+ counts <200 cells/μL. Fifty patients (46%) had CD4+ counts <50 cells/μL. Only 50 patients (37%) received antiretroviral therapy. Twenty one patients (16%) died during hospital stay. All but one deaths were due to TB (16 patients; 76%) and PCP (4 patients; 19%). CONCLUSIONS: A wide spectrum of disease, including both OIs and non-infectious opportunistic diseases, is seen in hospitalised HIV-infected patients from north India. Tuberculosis remains the most common OI and is the commonest cause of death in these patients

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients