Multivariate pattern classification of pediatric Tourette syndrome using functional connectivity MRI

Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics. Individuals with TS would benefit greatly from advances in prediction of symptom timecourse and treatment effectiveness. As a first step, we applied a multivariate method - support vector machine (SVM) classification - to test whether patterns in brain network activity, measured with resting state functional connectivity (RSFC) MRI, could predict diagnostic group membership for individuals. RSFC data from 42 children with TS (8-15 yrs) and 42 unaffected controls (age, IQ, in-scanner movement matched) were included. While univariate tests identified no significant group differences, SVM classified group membership with ~70% accuracy (p < .001). We also report a novel adaptation of SVM binary classification that, in addition to an overall accuracy rate for the SVM, provides a confidence measure for the accurate classification of each individual. Our results support the contention that multivariate methods can better capture the complexity of some brain disorders, and hold promise for predicting prognosis and treatment outcome for individuals with TS

Trend-TDT – a transmission/disequilibrium based association test on functional mini/microsatellites

<p>Abstract</p> <p>Background</p> <p>Minisatellites and microsatellites are associated with human disease, not only as markers of risk but also involved directly in disease pathogenesis. They may play significant roles in replication, repair and mutation of DNA, regulation of gene transcription and protein structure alteration. Phenotypes can thus be affected by mini/microsatellites in a manner proportional to the length of the allele. Here we propose a new method to assess the linear trend toward transmission of shorter or longer alleles from heterozygote parents to affected child.</p> <p>Results</p> <p>This test (trend-TDT) performs better than other TDT (Transmission/Disequilibrium Test) type tests, such as TDT_maxand TDT_L/S, under most marker-disease association models.</p> <p>Conclusion</p> <p>The trend-TDT test is a more powerful association test when there is a biological basis to suspect a relationship between allele length and disease risk.</p

Pest population dynamics are related to a continental overwintering gradient

Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests

DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases

Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient's mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer's drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction

The BARRIERS scale -- the barriers to research utilization scale: A systematic review

<p>Abstract</p> <p>Background</p> <p>A commonly recommended strategy for increasing research use in clinical practice is to identify barriers to change and then tailor interventions to overcome the identified barriers. In nursing, the BARRIERS scale has been used extensively to identify barriers to research utilization.</p> <p>Aim and objectives</p> <p>The aim of this systematic review was to examine the state of knowledge resulting from use of the BARRIERS scale and to make recommendations about future use of the scale. The following objectives were addressed: To examine how the scale has been modified, to examine its psychometric properties, to determine the main barriers (and whether they varied over time and geographic locations), and to identify associations between nurses' reported barriers and reported research use.</p> <p>Methods</p> <p>Medline (1991 to September 2009) and CINHAL (1991 to September 2009) were searched for published research, and ProQuest^®digital dissertations were searched for unpublished dissertations using the BARRIERS scale. Inclusion criteria were: studies using the BARRIERS scale in its entirety and where the sample was nurses. Two authors independently assessed the study quality and extracted the data. Descriptive and inferential statistics were used.</p> <p>Results</p> <p>Sixty-three studies were included, with most using a cross-sectional design. Not one study used the scale for tailoring interventions to overcome identified barriers. The main barriers reported were related to the setting, and the presentation of research findings. Overall, identified barriers were consistent over time and across geographic locations, despite varying sample size, response rate, study setting, and assessment of study quality. Few studies reported associations between reported research use and perceptions of barriers to research utilization.</p> <p>Conclusions</p> <p>The BARRIERS scale is a nonspecific tool for identifying general barriers to research utilization. The scale is reliable as reflected in assessments of internal consistency. The validity of the scale, however, is doubtful. There is no evidence that it is a useful tool for planning implementation interventions. We recommend that no further descriptive studies using the BARRIERS scale be undertaken. Barriers need to be measured specific to the particular context of implementation and the intended evidence to be implemented.</p

Testing mutual exclusivity of ETS rearranged prostate cancer

Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 5′ fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements