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Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science's grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain's structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and 'map' them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

This primer provides an overview of current practices in this emerging field and looks toward the future in the evolution and development of smartphone applications for the transportation sector. The primer provides an introduction and overview smartphone applications (known as “apps”); discusses the background, evolution, and development of smartphone apps; reviews the types of smartphone applications promoting transportation efficiency and congestion reduction; discusses transportation apps and their impacts on traveler behavior; examines current challenges; and concludes with guiding principles for public agencies.

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicines clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves.

Shared mobility - the shared use of a vehicle, bicycle, or other mode - enables users to gain short-term access to transportation modes on an “as-needed” basis. Shared mobility includes carsharing, bikesharing, ridesharing, and on-demand ride services. It can also include alternative transit services, such as paratransit, shuttles, and private transit services. Smartphone “apps” are available to aggregate options and optimize routes. New ways of transporting and delivering goods also have emerged with the potential to change the nature of the package and food delivery industry. Shared mobility has had a transformative impact on many global cities by enhancing transportation accessibility, while simultaneously reducing driving and personal vehicle ownership. This white paper provides an introduction and background to different types of shared modes, as well as smartphone-based trip planning apps that can facilitate access to public transit and shared mobility services. It also notes where potential benefits of shared mobility could align with the new mission of the California Department of Transportation (Caltrans).

Compassion is an affective response to another's suffering and a catalyst of prosocial behavior. In the present studies, we explore the peripheral physiological changes associated with the experience of compassion. Guided by long-standing theoretical claims, we propose that compassion is associated with activation in the parasympathetic autonomic nervous system through the vagus nerve. Across 4 studies, participants witnessed others suffer while we recorded physiological measures, including heart rate, respiration, skin conductance, and a measure of vagal activity called respiratory sinus arrhythmia (RSA). Participants exhibited greater RSA during the compassion induction compared with a neutral control (Study 1), another positive emotion (Study 2), and a prosocial emotion lacking appraisals of another person's suffering (Study 3). Greater RSA during the experience of compassion compared with the neutral or control emotion was often accompanied by lower heart rate and respiration but no difference in skin conductance. In Study 4, increases in RSA during compassion positively predicted an established composite of compassion-related words, continuous self-reports of compassion, and nonverbal displays of compassion. Compassion, a core affective component of empathy and prosociality, is associated with heightened parasympathetic activity.

Public bikesharing—the shared use of a bicycle fleet by the public—is an innovative mobility strategy that has recently emerged in major North American cities. Bikesharing systems typically position bicycles throughout an urban environment, among a network of docking stations, for immediate access. This paper discusses the modal shift that results from individuals participating in four public bikesharing systems in North America. The authors conducted an online survey (n =10,661 total sample), between November 2011 and January 2012, with members of four major bikesharing organizations (located in Montreal, Toronto, the Twin Cities, and Washington D.C.) and collected information regarding travel-behavior changes, focusing on modal shift, as well as public bikesharing perceptions. The survey probed member perceptions about bikesharing and found that a majority in the surveyed cities felt that bikesharing was an enhancement to public transportation and improved transit connectivity. With respect to modal shift, the results suggest that bikesharing generally draws from all travel modes. Three of the four largest cities in the study exhibited declines in bus and rail usage as a result of bikesharing. For example, 50% of respondents in Montreal reported reducing rail use, while 44% and 48% reported similar shifts in Toronto and Washington D.C., respectively. However, within those same cities, 27% to 40% of respondents reported using public transit in conjunction with bikesharing to make trips previously completed by automobile. In the Twin Cities, the dynamic was different, as 15% of respondents reported increasing rail usage versus only 3% who noted a decrease in rail use. In all cities, bikesharing resulted in a considerable decline in personal driving and taxi use, suggesting that public bikesharing is reducing urban transportation emissions, while at the same time freeing capacity of bus and rail networks within large cities.

Although histopathological diagnosis is essential in decision of therapeutic strategy for gliomas, sometimes the tumors diagnosed in one histological entity show thoroughly different clinical courses. This phenomenon is believed to be due primarily to the presence of the genetic subgroup. In fact, relationship between treatment response and certain genetic characteristics is indicated (e.g. better chemosensitivity in glioma with losses of 1p/19q (−1p/19q)). It is highly likely that genetic classification of glioma is useful to select the adjuvant treatment. Additionally, gain of 7q (+7q) and −1p/19q are early events in 2 distinct tumor lineages, astrocytic tumors and oligodendroglial tumors, respectively, and these tumors obtain additional genetic aberration (−9p, 10q) with tumor progression. On the other hand, concerning the tumors without +7q or −1p/19q, little is known about clinically important genetic aberration. Therefore the study on such tumors could provide useful information for the prognosis prediction and the determination of treatment strategy. METHODS: We selected 39 cases of gliomas without +7q or −1p/19q from 200 adult supratentorial glioma cases surgically treated and analyzed chromosomal DNA copy number aberrations (CNAs) by comparative genomic hybridization (CGH) from 2005 to 2012. We correlated clinical features of these tumors with histological characteristics, CNAs and IDH1 status. RESULTS: The clinical course of gliomas without +7q or −1p/19q was not correlated with additional genetic aberration of -9p or 10q, which have been known as genetic markers for poor prognosis, and absence of +7q or −1p/19q was maintained at the time of recurrence. The tumors without +7q or −1p/19q showed relatively favorable prognosis although mutation of IDH1 was infrequent in these tumors (35.8 %). CONCLUSION: The gliomas without +7q or −1p/19q have clinical features distinct from the +7q and −1p/19q gliomas. Prognostic markers for each subgroups could help establish therapeutic strategy against the tumor. DNA methylation is a mechanism altering the normal state of cells implicated in many cancers. Currently the methylation status of MGMT is one of the most widely utilized clinical genetic tests performed on glioblastoma multiforme (GBM). While several global gene expression signatures have been developed, it is unclear if genome-wide DNA methylation signatures can predict prognosis in cancer. We used a computational algorithm (MethylMix) to analyze genome-wide DNA methylation in GBM data obtained from The Cancer Genome Atlas (TCGA). MethylMix identified a set of driver genes that met criteria for being both differential and functional. Differential refers to a difference in cancer methylation compared to normal tissue; functional refers to having a significant correlation with matched gene expression changes. We then used these MethylMix driver genes to build multivariate models of overall survival using linear regression and validated these models in independent data sets. Applying MethylMix and linear regression we identified a novel methylation signature predictive of overall survival, which we here define as the GLIOMETH signature. Interestingly, GLIOMETH did not include MGMT, suggesting that MGMT methylation is not essential to predict prognosis in GBM. GLIOMETH was prognostically significant even in a multivariate analysis with known prognostic covariates, including MGMT methylation. We validated GLIOMETH in two external DNA methylation data sets and two gene expression data sets, using a leveraging technique predicting methylation in terms of gene expression, showing also a significant survival correlation. Differential and functional DNA methylation is predictive of overall survival in GBM independent of known prognostic factors. We identified GLIOMETH as a DNA methylation signature that is predictive of overall survival in GBM, outperforming MGMT methylation. The GLIOMETH model validated across multiple independent DNA methylation and gene expression validation data sets demonstrating its robustness as an independent predictor of prognosis in GBM. Recent next-generation genomic studies of medulloblastoma have revealed an unexpected and overwhelming convergence of somatic alterations affecting chromatin-modifying genes. Estimates informed by next-generation sequencing implicate that at least one third of all medulloblastomas have somatic mutations in a chromatin modifier, including those targeting histone methyltransfereses, histone demethylases, and related chromatin modulators that collectively function to influence chromatin conformation associated gene expression states. These mutations occur across all four medulloblastoma subgroups although different sets of genes appear to be selectively altered in a subgroup-specific manner. Despite the abundance of evidence implicating deregulation of chromatin modifiers as a key event in medulloblastoma pathogenesis, the medulloblastoma epigenome remains largely unexplored, and studies cataloguing histone modification states on a genome-wide scale have yet to be reported. To comprehensively investigate the histone code in medulloblastoma and the consequences associated with mutations affecting histone-modifying genes, we have performed ChIP-sequencing on a set of well-characterized primary medulloblastoma specimens. Histone marks examined in this study include the six modifications mandated by the International Human Epigenome Consortium (IHEC), including H3K4me3, H3K9me3, H3K27me3, H3K27ac, H3K4me1 and H3K36me3. Chromatin isolates from primary fresh-frozen tissues representative of each medulloblastoma subgroup were immunoprecipitated with the indicated antibodies and sequenced with a HiSeq Illumina sequencer to obtain at least 10 million unique reads per ChIP experiment. Peak calling was performed using multiple publicly available tools and data integrated with existing ENCODE data for the same histone marks. Inter-subgroup comparisons of histone modification states revealed a wealth of distinguishing genomic regions that were highly correlated with alternative patterns of gene expression existing between the subgroups. Moreover, integration with existing mutational profiles demonstrated aberrant chromatin states that could be linked to underlying mutations in select chromatin modifiers. Ongoing work will focus on expanding the cohort and integration with all levels of ‘omic data.

Since the mid-2000s, public bikesharing (also known as ‘‘bike hire’’) has developed and spread into a new form of mobility in cities across the globe. This paper presents an analysis of the recent increase in the number of public bikesharing systems. Bikesharing is the shared use of a bicycle fleet, which is accessible to the public and serves as a form of public transportation. The initial system designs were pioneered in Europe and, after a series of technological innovations, appear to have matured into a system experiencing widespread adoption. There are also signs that the policy of public bikesharing systems is transferable and is being adopted in other contexts outside Europe. In public policy, the technologies that are transferred can be policies, technologies, ideals or systems. This paper seeks to describe the nature of these systems, how they have spread in time and space, how they have matured in different contexts, and why they have been adopted.            Researchers provide an analysis from Europe and North America. The analysis draws on published data sources, a survey of 19 systems, and interviews with 12 decision-makers in Europe and 14 decision-makers in North America. The data are examined through the lens of diffusion theory, which allows for comparison of the adoption process in different contexts. A mixture of quantitative and qualitative analyses is used to explore the reasons for adoption decisions in different cities. The paper concludes that Europe is still in a major adoption process with new systems emerging and growth in some existing systems, although some geographic areas have adopted alternative solutions. Private sector operators have also been important entrepreneurs in a European context, which has accelerated the uptake of these systems. In North America, the adoption process is at an earlier stage and is gaining momentum, but signs also suggest the growing importance of entrepreneurs in North America with respect to technology and business models. There is evidence to suggest that the policy adoption processes have been inspired by successful systems in Paris, Lyon, Montreal, and Washington, DC, for instance, and that diffusion theory could be useful in understanding public bikesharing policy adoption in a global context.

Public bikesharing—the shared use of a bicycle fleet by the public—is an innovative mobility strategy that has recently emerged in major North American cities. Bikesharing systems typically position bicycles throughout an urban environment, among a network of docking stations, for immediate access. Approximately five years ago, information technology (or IT)-based bikesharing services began to emerge in North America. Between 2007 and March 2013, 28 IT-based programs have been deployed–24 are operational, two are temporarily suspended, and two are now defunct in the United States (U.S.) and Canada. Bikesharing growth potential in North America is examined on the basis of a survey of all 15 IT-based public bikesharing systems operating in the U.S. and all four programs deployed in Canada, as of January 2012. These programs accounted for 172,070 users and 5,238 bicycles and 44,352 users and 6,235 bicycles in the U.S. and Canada, respectively, in January 2012. This paper reviews early operator understanding of North American public bikesharing and discusses emerging trends for prospective program start-ups.Public bikesharing—the shared use of a bicycle fleet by the public—is an innovative mobility strategy that has recently emerged in major North American cities. Bikesharing systems typically position bicycles throughout an urban environment, among a network of docking stations, for immediate access. Approximately five years ago, information technology (or IT)-based bikesharing services began to emerge in North America. Between 2007 and March 2013, 28 IT-based programs have been deployed–24 are operational, two are temporarily suspended, and two are now defunct in the United States (U.S.) and Canada. Bikesharing growth potential in North America is examined on the basis of a survey of all 15 IT-based public bikesharing systems operating in the U.S. and all four programs deployed in Canada, as of January 2012. These programs accounted for 172,070 users and 5,238 bicycles and 44,352 users and 6,235 bicycles in the U.S. and Canada, respectively, in January 2012. This paper reviews early operator understanding of North American public bikesharing and discusses emerging trends for prospective program start-ups.

Carsharing (or short-term auto use) provides a flexible alternative that meets diverse transportation needs across the globe, while reducing the negative impacts of private vehicle ownership. More than 65 years ago, carsharing began appearing in Europe. It has expanded to approximately 1,100 cities worldwide, in 26 nations on five continents. This article provides a global perspective of carsharing growth and future developments from 2006 through 2015, employing data from three surveys conducted in 2006, 2008, and 2010. The authors explore the interview findings of 25 carsharing experts worldwide representing 25 of 26 nations, collected in 2010.

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ≥1 dose increased from 38% to 97%. Case-control VE for ≥1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ≥1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs.

Carsharing provides users access to a shared vehicle fleet for short-term use throughout the day, reducing the need for private vehicles. The provision of on-street and public off-street parking dedicated to carsharing is an important policy area confronting public agencies. As of July 2009, approximately 377,600 individuals were carsharing members in North America in about 57 metropolitan areas. A total of 17 jurisdictions, one state (California), and eight public transit operators in North America have formal and informal carsharing parking policies, pilot projects, and proposed legislation. These are reviewed in this paper, along with a framework for carsharing parking policy that reflects three levels of governmental support.In addition, the authors examine carsharing parking policies in three jurisdictions in the San Francisco Bay Area, which accounts for an estimated 50,000 carsharing members and 1,100 shared-use vehicles. Supporting this examination is an intercept survey on carsharing parking (n=425) conducted in the Bay Area. Results show that most people supported the conversion of some type of spaces for carsharing use, and 48% thought that carsharing organizations should compensate the city for on-street spaces. At the same time, converting most types of spaces was opposed by at least 20% of respondents. Neighborhood residents were generally more in favor of parking conversion for carsharing than people visiting the area for work or errands. Finally, a majority (61%) felt that non-profits should have priority over for-profit organizations for carsharing spaces and should pay less than for-profit organizations.

Carsharing provides users access to a shared vehicle fleet for short-term use throughout the day, reducing the need for private vehicles. The provision of on-street and public off-street parking dedicated to carsharing is an important policy area confronting public agencies. As of July 2009, approximately 377,600 individuals were carsharing members in North America in about 57 metropolitan areas. A total of 17 jurisdictions, one state (California), and eight public transit operators in North America have formal and informal carsharing parking policies, pilot projects, and proposed legislation. These are reviewed in this paper, along with a framework for carsharing parking policy that reflects three levels of governmental support. In addition, the authors examine carsharing parking policies in three jurisdictions in the San Francisco Bay Area, which accounts for an estimated 50,000 carsharing members and 1,100 shared-use vehicles. Supporting this examination is an intercept survey on carsharing parking (n=425) conducted in the Bay Area. Results show that most people supported the conversion of some type of spaces for carsharing use, and 48% thought that carsharing organizations should compensate the city for on-street spaces. At the same time, converting most types of spaces was opposed by at least 20% of respondents. Neighborhood residents were generally more in favor of parking conversion for carsharing than people visiting the area for work or errands. Finally, a majority (61%) felt that non-profits should have priority over for-profit organizations for carsharing spaces and should pay less than for-profit organizations.

Carsharing organizations (or short-term auto use) provide members access to a fleet of shared vehicles on an hourly basis, reducing the need for private vehicle ownership. This paper reflects a ten-year retrospective of carsharing in Canada and the United States (U.S.), including results from a 2008 operator survey. Since 1994, a total of 50 carsharing programs have been deployed in North America⎯33 are operational, and 17 are defunct. As of July 1, 2008, there were 14 active programs in Canada and 19 in the U.S., with approximately 319,000 carsharing members sharing over 7,500 vehicles in North America. Another six programs were planned to launch in North America by January 2009. The four largest providers in the U.S. and Canada support 99% and 95.2% of total membership, respectively.In this ten-year retrospective, the authors examine North America’s carsharing evolution from initial market entry and experimentation (1994 to mid-2002) to growth and market diversification (mid-2002 to late-2007) to commercial mainstreaming (late-2007 to present). This evolution includes increased competition, new market entrants, program consolidation, increased market diversification, capital investment, technological advancement, and greater inter-operator collaboration. Ongoing growth and competition are forecasted. Rising fuel costs and increased climate change awareness will likely facilitate this expansion.