Two-Dimensional Partial-Covariance Mass Spectrometry of Large Molecules Based on Fragment Correlations

Covariance mapping [L. J. Frasinski, K. Codling, and P. A. Hatherly, Science 246, 1029 (1989)] is a well-established technique used for the study of mechanisms of laser-induced molecular ionization and decomposition. It measures statistical correlations between fluctuating signals of pairs of detected species (ions, fragments, electrons). A positive correlation identifies pairs of products originating from the same dissociation or ionization event. A major challenge for covariance-mapping spectroscopy is accessing decompositions of large polyatomic molecules, where true physical correlations are overwhelmed by spurious signals of no physical significance induced by fluctuations in experimental parameters. As a result, successful applications of covariance mapping have so far been restricted to low-mass systems, e.g., organic molecules of around 50 daltons (Da). Partial-covariance mapping was suggested to tackle the problem of spurious correlations by taking into account the independently measured fluctuations in the experimental conditions. However, its potential has never been realized for the decomposition of large molecules, because in these complex situations, determining and continuously monitoring multiple experimental parameters affecting all the measured signals simultaneously becomes unfeasible. We introduce, through deriving theoretically and confirming experimentally, a conceptually new type of partial-covariance mapping—self-correcting partial-covariance spectroscopy—based on a parameter extracted from the measured spectrum itself. We use the readily available total ion count as the self-correcting partial-covariance parameter, thus eliminating the challenge of determining experimental parameter fluctuations in covariance measurements of large complex systems. The introduced self-correcting partial covariance enables us to successfully resolve correlations of molecules as large as 10 3 – 10 4     Da , 2 orders of magnitude above the state of the art. This opens new opportunities for mechanistic studies of large molecule decompositions through revealing their fragment-fragment correlations. Moreover, we demonstrate that self-correcting partial covariance is applicable to solving the inverse problem: reconstruction of a molecular structure from its fragment spectrum, within two-dimensional partial-covariance mass spectrometry

Using Search Query Surveillance to Monitor Tax Avoidance and Smoking Cessation following the United States' 2009 “SCHIP” Cigarette Tax Increase

Smokers can use the web to continue or quit their habit. Online vendors sell reduced or tax-free cigarettes lowering smoking costs, while health advocates use the web to promote cessation. We examined how smokers' tax avoidance and smoking cessation Internet search queries were motivated by the United States' (US) 2009 State Children's Health Insurance Program (SCHIP) federal cigarette excise tax increase and two other state specific tax increases. Google keyword searches among residents in a taxed geography (US or US state) were compared to an untaxed geography (Canada) for two years around each tax increase. Search data were normalized to a relative search volume (RSV) scale, where the highest search proportion was labeled 100 with lesser proportions scaled by how they relatively compared to the highest proportion. Changes in RSV were estimated by comparing means during and after the tax increase to means before the tax increase, across taxed and untaxed geographies. The SCHIP tax was associated with an 11.8% (95% confidence interval [95%CI], 5.7 to 17.9; p<.001) immediate increase in cessation searches; however, searches quickly abated and approximated differences from pre-tax levels in Canada during the months after the tax. Tax avoidance searches increased 27.9% (95%CI, 15.9 to 39.9; p<.001) and 5.3% (95%CI, 3.6 to 7.1; p<.001) during and in the months after the tax compared to Canada, respectively, suggesting avoidance is the more pronounced and durable response. Trends were similar for state-specific tax increases but suggest strong interactive processes across taxes. When the SCHIP tax followed Florida's tax, versus not, it promoted more cessation and avoidance searches. Efforts to combat tax avoidance and increase cessation may be enhanced by using interventions targeted and tailored to smokers' searches. Search query surveillance is a valuable real-time, free and public method, that may be generalized to other behavioral, biological, informational or psychological outcomes manifested online

Inevitable Evolutionary Temporal Elements in Neural Processing: A Study Based on Evolutionary Simulations

Recent studies have suggested that some neural computational mechanisms are based on the fine temporal structure of spiking activity. However, less effort has been devoted to investigating the evolutionary aspects of such mechanisms. In this paper we explore the issue of temporal neural computation from an evolutionary point of view, using a genetic simulation of the evolutionary development of neural systems. We evolve neural systems in an environment with selective pressure based on mate finding, and examine the temporal aspects of the evolved systems. In repeating evolutionary sessions, there was a significant increase during evolution in the mutual information between the evolved agent's temporal neural representation and the external environment. In ten different simulated evolutionary sessions, there was an increased effect of time -related neural ablations on the agents' fitness. These results suggest that in some fitness landscapes the emergence of temporal elements in neural computation is almost inevitable. Future research using similar evolutionary simulations may shed new light on various biological mechanisms

The effects of timing of fine needle aspiration biopsies on gene expression profiles in breast cancers

<p>Abstract</p> <p>Background</p> <p>DNA microarray analysis has great potential to become an important clinical tool to individualize prognostication and treatment for breast cancer patients. However, with any emerging technology, there are many variables one must consider before bringing the technology to the bedside. There are already concerted efforts to standardize protocols and to improve reproducibility of DNA microarray. Our study examines one variable that is often overlooked, the timing of tissue acquisition, which may have a significant impact on the outcomes of DNA microarray analyses especially in studies that compare microarray data based on biospecimens taken <it>in vivo </it>and <it>ex vivo</it>.</p> <p>Methods</p> <p>From 16 patients, we obtained paired fine needle aspiration biopsies (FNABs) of breast cancers taken before (PRE) and after (POST) their surgeries and compared the microarray data to determine the genes that were differentially expressed between the FNABs taken at the two time points. qRT-PCR was used to validate our findings. To examine effects of longer exposure to hypoxia on gene expression, we also compared the gene expression profiles of 10 breast cancers from clinical tissue bank.</p> <p>Results</p> <p>Using hierarchical clustering analysis, 12 genes were found to be differentially expressed between the FNABs taken before and after surgical removal. Remarkably, most of the genes were linked to FOS in an early hypoxia pathway. The gene expression of FOS also increased with longer exposure to hypoxia.</p> <p>Conclusion</p> <p>Our study demonstrated that the timing of fine needle aspiration biopsies can be a confounding factor in microarray data analyses in breast cancer. We have shown that FOS-related genes, which have been implicated in early hypoxia as well as the development of breast cancers, were differentially expressed before and after surgery. Therefore, it is important that future studies take timing of tissue acquisition into account.</p

Health Disparities Between Appalachian and Non-Appalachian Counties in Virginia USA

The examination of health disparities among people within Appalachian counties compared to people living in other counties is needed to find ways to strategically target improvements in community health in the United States of America (USA). Methods: A telephone survey of a random sample of adults living in households within communities of all counties of the state of Virginia (VA) in the USA was conducted. Findings: Health status was poorer among those in communities within Appalachian counties in VA and health insurance did not make a difference. Health perception was significantly worse in residents within communities in Appalachian counties compared to non-Appalachian community residents (30.5 vs. 17.4% rated their health status as poor/fair), and was worse even among those with no chronic diseases. Within communities in Appalachian counties, black residents report significantly better health perception than do white residents. Conclusion: Residents living in communities in Appalachian counties in VA are not receiving adequate health care, even among those with health insurance. More research with a larger ethnic minority sample is needed to investigate the racial/ethnic disparities in self-reported health and health care utilization within communities

Abordagem da artroplastia total do joelho no Brasil: estudo transversal

CONTEXT AND OBJECTIVE: Total knee arthroplasty (TKA) has evolved particularly since the 1970s, with improvements in implants and surgical instruments, and has thus become an effective intervention for treating knee arthrosis. Many studies have presented rates of satisfactory clinical and radiological results greater than 90%, from follow-ups of over ten years. Nevertheless, despite scientific evidence showing the efficacy of TKA, the approaches taken present controversies in certain respects. The objective of this study was to evaluate how the Brazilian orthopedists deal with TKA, with investigation of the main aspects of this procedure. DESIGN AND SETTING: Cross-sectional survey conducted during the 39th Brazilian Congress of Orthopedics and Traumatology, in São Paulo, Brazil, in November 2007. METHODS: We applied a questionnaire to orthopedists registered at the congress. The questionnaire was randomly distributed and participation was voluntary; 858 completed questionnaires were included in the analysis. RESULTS: Most of the Brazilian orthopedists were members of SBOT and worked in the southeastern region. They used imported cemented implants through an anterior access route centered on the patella, with replacement of the joint surface of the patella and preservation of the posterior cruciate ligament. They did not have experience with simultaneous bilateral TKA. Postoperatively, they used antibiotics and suction drains for 48 hours. There was no consensus regarding prophylaxis for venous thromboembolism or the frequency of the main complications. CONCLUSION: The majority of Brazilian orthopedists work in the southeastern region of the country and agree about the main aspects of the approaches towards TKA.CONTEXTO E OBJETIVO: A artroplastia total do joelho (ATJ) evoluiu sobremaneira desde os anos 70, com melhora dos implantes e do instrumental cirúrgico, tornando-se uma intervenção efetiva para o tratamento da artrose do joelho. Muitos estudos apresentam resultados clínicos e radiológicos satisfatórios superiores a 90% no acompanhamento acima de 10 anos. Apesar das evidências científicas sobre sua eficácia da ATJ, a sua abordagem apresenta controvérsias em alguns aspectos. O objetivo do estudo foi avaliar como o ortopedista brasileiro aborda a ATJ e os principais aspectos técnicos na realização deste procedimento. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado durante o 39º Congresso Brasileiro de Ortopedia e Traumatologia em São Paulo, Brasil, em novembro de 2007. MÉTODOS: Aplicamos um questionário aos ortopedistas inscritos no congresso. A distribuição foi aleatória com adesão voluntária. Foram incluídos 858 questionários para análise. RESULTADOS: A maioria dos Ortopedistas Brasileiros são membros da SBOT e atua na região sudeste. Usam o implante importado, cimentado, por via de acesso anterior centrada na patela, com substituição da superfície articular da patela e preservação do ligamento cruzado posterior e não tem experiência com a artroplastia total bilateral simultânea. No pós-operatório utilizam antibióticos e dreno de sucção por 48 horas. Não houve consenso quanto à profilaxia para tromboembolismo venoso e frequência das principais complicações. CONCLUSÃO: A maioria dos ortopedistas brasileiros trabalha na região sudeste e concorda quanto aos principais aspectos da abordagem da ATJ.Universidade Federal de São Paulo (UNIFESP) Department of Orthopedics and TraumatologyUniversidade Federal de São Paulo (UNIFESP) Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupUNIFESP, Department of Orthopedics and TraumatologyUNIFESP, Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupSciEL

A randomized controlled trial testing the effectiveness of a universal school-based depression prevention program 'Op Volle Kracht' in the Netherlands

Contains fulltext : 102521.pdf (publisher's version ) (Open Access)Background: The incidence of depressive symptoms increases during adolescence, from 10.0% to 24.5% at age 11 to 15, respectively. Experiencing elevated levels of depressive symptoms increases the risk of a depressive disorder in adulthood. A universal school-based depression prevention program Op Volle Kracht (OVK) was developed, based on the Penn Resiliency Program, aimed at preventing the increase of depressive symptoms during adolescence and enhancing positive development. In this study the effectiveness of OVK will be tested and possible mediators of program effects will be focus of study as well. Method: The effectiveness of OVK will be tested in a randomized controlled trial with two conditions, intervention (OVK) and control condition (care as usual). Schools are randomly assigned to research conditions. OVK will be incorporated in the school curriculum, maximizing program attendance. OVK consists of 16 lessons of 50 min, given by trained psychologists to groups of 11-15 students. OVK contains Cognitive Behavioral Therapy, social skills training, problem solving and decision making. Outcomes are measured at 6, 12, 18 and 24 months follow up, to monitor long term program effects. Primary outcome is level of depressive symptoms, secondary outcomes are: anxiety, hopelessness, cognitive bias, substance use, truancy, life satisfaction, coping, self-efficacy, optimism, happiness, friendship, school performance and school attitude. The questionnaires for students will be administered in the school setting. Parents will complete a questionnaire at baseline only. Discussion: In this paper the study into the effectiveness of the depression prevention program OVK was described. It is expected that OVK will prevent the increase in depressive symptoms during adolescence and enhance positive development in the intervention condition, compared to the control condition. If OVK will be effective, it can be implemented in the school context by which numerous adolescents can be reached.9 p

Lifecourse socioeconomic circumstances and multimorbidity among older adults

<p>Abstract</p> <p>Background</p> <p>Many older adults manage multiple chronic conditions (i.e. multimorbidity); and many of these chronic conditions share common risk factors such as low socioeconomic status (SES) in adulthood and low SES across the lifecourse. To better capture socioeconomic condition in childhood, recent research in lifecourse epidemiology has broadened the notion of SES to include the experience of specific hardships. In this study we investigate the association among childhood financial hardship, lifetime earnings, and multimorbidity.</p> <p>Methods</p> <p>Cross-sectional analysis of 7,305 participants age 50 and older from the 2004 Health and Retirement Study (HRS) who also gave permission for their HRS records to be linked to their Social Security Records in the United States. Zero-inflated Poisson regression models were used to simultaneously model the likelihood of the absence of morbidity and the expected number of chronic conditions.</p> <p>Results</p> <p>Childhood financial hardship and lifetime earnings were not associated with the absence of morbidity. However, childhood financial hardship was associated with an 8% higher number of chronic conditions; and, an increase in lifetime earnings, operationalized as average annual earnings during young and middle adulthood, was associated with a 5% lower number of chronic conditions reported. We also found a significant interaction between childhood financial hardship and lifetime earnings on multimorbidity.</p> <p>Conclusions</p> <p>This study shows that childhood financial hardship and lifetime earnings are associated with multimorbidity, but not associated with the absence of morbidity. Lifetime earnings modified the association between childhood financial hardship and multimorbidity suggesting that this association is differentially influential depending on earnings across young and middle adulthood. Further research is needed to elucidate lifecourse socioeconomic pathways associated with the absence of morbidity and the presence of multimorbidity among older adults.</p

Protein Signature of Lung Cancer Tissues

Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment