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Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059–0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55–74 at enrollment in 1993–2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

We present a 368 ks deep Chandra observation of Abell 1240, a binary merging galaxy cluster at a redshift of 0.195 with two brightest cluster galaxies that may have passed each other 0.3 Gyr ago. Building upon previous investigations involving Giant Metrewave Radio Telescope, Very Large Array, and LOFAR data, our study focuses on two prominent extended radio relics at the northwest (NW) and southeast (SE) of the cluster core. By leveraging the high-resolution Chandra imaging, we have identified two distinct surface-brightness edges at ∼1 Mpc and 1.2 Mpc NW and SE of the cluster center, respectively, coinciding with the outer edges of both relics. Our temperature measurements suggest the edges to be shock front edges. The Mach numbers, derived from the gas density jumps, yield ${{ \mathcal M }}_{\mathrm{SE}}$ = ${1.49}_{-0.24}^{+0.22}$ for the SE shock and ${{ \mathcal M }}_{\mathrm{NW}}$ = ${1.41}_{-0.19}^{+0.17}$ for the NW shock. Our estimated Mach numbers are remarkably smaller compared to those derived from radio observations ( ${{ \mathcal M }}_{\mathrm{SE}}$ = 2.3 and ${{ \mathcal M }}_{\mathrm{NW}}$ = 2.4), highlighting the prevalence of a reacceleration scenario over direct acceleration of electrons from the thermal pool. Furthermore, we compare the observed temperature profiles across both shocks with those of predictions from collisional versus collisionless models. Both shocks favor the Coulomb collisional model, but we could not rule out a purely collisionless model due to pre-shock temperature uncertainties.

Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any prognostic or predictive value. Thus, current cfDNA testing cannot be relied upon for perioperative risk stratification (POR), including early detection of recurrence, long-term surveillance, predicting outcomes, and treatment response. Prior evidence on cfDNA mutation profiling (non-specific detection or gene panel testing) suggests that it can be a reliable tool for POR and prognostication, but it still requires significant improvements. cfDNA methylation changes or epigenetic markers have not been explored extensively, but early studies have shown potential for it to be a prognostic biomarker tool. The predictive value of cfDNA (mutations and EM) to assist treatment selection (systemic therapy, immune-checkpoint inhibitor vs. tyrosine kinase inhibitor) and to monitor response to systemic and locoregional therapies should be a future area of focus. We highlighted the unmet needs in the HCC management and the current role of cfDNA testing in HCC in addressing them.

Background: Radiation-induced hypothyroidism is a common toxicity of head and neck radiation. Our re-planning study aimed to reduce thyroid dose while maintaining target coverage with IMRT. Methods: We retrospectively identified patients with oral-cavity (n = 5) and oropharyngeal cancer (n = 5). Treatment plans were re-optimized with 45 Gy thyroid mean dose constraint, then we cropped the thyroid out of PTVs and further reduced thyroid dose. Target coverage was delivering 100% dose to ≥ 93% of PTV and 95% of dose to > 99% of PTV. Results: Originally, average mean dose to thyroid was 5580 cGy. In model I, this dropped to 4325 cGy (p

Abstract Background The heterogeneity of the breast tumor microenvironment (TME) may contribute to the lack of durable responses to immune checkpoint blockade (ICB); however, mouse models to test this are currently lacking. Proper selection and use of preclinical models are necessary for rigorous, preclinical studies to rapidly move laboratory findings into the clinic. Methods Three versions of a common syngeneic model derived from the MMTV-PyMT autochthonous model were generated by inoculating 1E6, 1E5, or 1E4 cells derived from the MMTV-PyMT mouse into wildtype recipient mice. To elucidate how tumor latency and TME heterogeneity contribute to ICB resistance, comprehensive characterization of the TME using quantitative flow-cytometry and RNA expression analysis (NanoString) was performed. Subsequently, response to ICB was tested. These procedures were repeated using the EMT6 breast cancer model. Results The 3 syngeneic versions of the MMTV-PyMT model had vastly different TMEs that correlated to ICB response. The number of cells used to generate syngeneic tumors significantly influenced tumor latency, infiltrating leukocyte populations, and response to ICB. These results were confirmed using the EMT6 breast cancer model. Compared to the MMTV-PyMT autochthonous model, all 3 MMTV-PyMT syngeneic models had significantly more tumor-infiltrating lymphocytes (TILs; CD3+, CD4+, and CD8+) and higher proportions of PD-L1-positive myeloid cells, whereas the MMTV-PyMT autochthonous model had the highest frequency of myeloid cells out of total leukocytes. Increased TILs correlated with response to anti-PD-L1 and anti-CTLA-4 therapy, but PD-L1expression on tumor cells or PD-1 expression of T cells did not. Conclusions These studies reveal that tumor cell number correlates with tumor latency, TME, and response to ICB. ICB-sensitive and resistant syngeneic breast cancer models were identified, in which the 1E4 syngeneic model was most resistant to ICB. Given the lack of benefit from ICB in breast cancer, identifying robust murine models presented here provides the opportunity to further interrogate the TME for breast cancer treatment and provide novel insights into therapeutic combinations to overcome ICB resistance.

There is ample evidence of the role of land use and transportation interactions in determining urban spatial structure. The increased digitization of human activity produces a wealth of new data that can support longitudinal studies of changes in land-value distributions and integrated urban microsimulation models. To produce a comprehensive dataset, information from various sources needs to be merged at the land-parcel level to enhance datasets with additional attributes, while maintaining the ease of data storage and retrieval and respecting spatial and temporal relationships. This paper proposes a prototype of a workflow to augment a historical dataset of real estate transactions with data from multiple urban sources and to use machine learning to classify land use of each record based on housing market dynamics. The study finds that engineered parcel-level attributes, capturing housing market dynamics, have stronger predictive power than aggregated socio-economic variables, for classifying property land use.

To capture the complex relationships between transportation and land use, researchers and practitioners are increasingly using place-based measures of transportation accessibility to support a broad range of planning goals. This research reviews the state-of-the-art in applied transportation accessibility measurement and performs a comparative evaluation of software tools for calculating accessibility by walking and public transit including ArcGIS Pro, Emme, R5R, and OpenTripPlanner using R and Python, among others. Using a case study of Toronto, we specify both origin-based and regional-scale analysis scenarios and find significant differences in computation time and calculated accessibilities. While the calculated travel time matrices are highly correlated across tools, each tool produces different results for the same origin-destination pair. Comparisons of the estimated accessibilities also reveal evidence of spatial clustering in the ways paths are calculated by some tools relative to others at different locations around the city. With the growing emphasis on accessibility-based planning, analysts should approach the calculation of accessibility with care and recognize the potential for algorithmic dependence in their calculated accessibility results.

Ankle–foot orthoses (AFOs) are prescribed to children with cerebral palsy (CP) in hopes of improving their gait and gross motor activities. The purpose of this retrospective study was to examine if clinically significant changes in gross motor function occur with the use of AFOs in children and adolescents diagnosed with CP (Gross Motor Function Classification System levels I and II). Data from 124 clinical assessments were analyzed. Based on minimum clinically important difference (MCID), 77% of subjects demonstrated an increase in stride length, 45% of subjects demonstrated an increase in walking velocity, and 30% demonstrated a decrease in cadence. Additionally, 27% of the subjects demonstrated increase in gait deviation index (GDI). Deterioration in gait was evident by decreases in walking speed (5% of subjects), increases in cadence (11% of subjects), and 15% of subjects demonstrated decreases in gait deviation index. Twenty-two percent of subjects demonstrated no change in stride lengths and one participant demonstrated a decrease in stride length. However, AFOs improved Gross Motor Function Measure (GMFM) scores for a minority (10%) of children with mild CP (GMFCS level I and II), with 82–85% of subjects demonstrating no change in GMFM scores and 5–7% demonstrating decrease in GMFM scores.

Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study, we investigate two factors that are predicted to influence the mutation rate: ecology and genome size. We conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact that ecology can have on the adaptive potential of bacterial pathogens. Author summary Mutations are the ultimate source of all genetic variation and mutation rates vary considerably both within and between bacterial species. Understanding the drivers of this variation is important as it influences the capacity of bacteria to respond to challenges. It is particularly important for bacterial pathogens as it impacts how they respond to host immune responses and antibiotic treatments. Our study investigates how mutation rates vary within a bacterial species that has both a variable genome size and a variable ecological relationship with its host. While inter-species comparisons have found that bacterial species with smaller genomes tend to have faster mutation rates, our within-species comparisons show no evidence of a link between mutation rate and genome size. Instead, we find that strains that were involved in invasive infections have faster mutation rates than those carried asymptomatically by a host. This suggests that different factors influence mutation rate variation over different timescales, and that short-term changes are sensitive to ecological transitions. This contributes to our understanding of both the adaptive potential of pathogens, and the obstacles that bacteria have to overcome to cause disease in their host.

The sharing of research data is essential to ensure reproducibility and maximize the impact of public investments in scientific research. Here, we describe OpenNeuro, a BRAIN Initiative data archive that provides the ability to openly share data from a broad range of brain imaging data types following the FAIR principles for data sharing. We highlight the importance of the Brain Imaging Data Structure standard for enabling effective curation, sharing, and reuse of data. The archive presently shares more than 600 datasets including data from more than 20,000 participants, comprising multiple species and measurement modalities and a broad range of phenotypes. The impact of the shared data is evident in a growing number of published reuses, currently totalling more than 150 publications. We conclude by describing plans for future development and integration with other ongoing open science efforts.

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community—biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations—to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.

Widespread adoption of heavy-duty (HD) electric vehicles (EVs) will soon necessitate the use of megawatt (MW)-scale charging stations to charge high-capacity HD EV battery packs. Such a station design needs to anticipate possible station traffic, average and peak power demand, and charging/wait time targets to improve throughput and maximize revenue-generating operations. High-power direct current charging is an attractive candidate for MW-scale charging stations at the time of this study, but there are no precedents for such a station design for HD vehicles. We present a modeling and data analysis framework to elucidate the dependencies of a MW-scale station operation on vehicle traffic data and station design parameters and how that impacts vehicle electrification. This framework integrates an agent-based charging station model with vehicle schedules obtained through real-world vehicle telemetry data analysis to explore the station design and operation space. A case study applies this framework to a Class 8 vehicle telemetry dataset and uses Monte Carlo simulations to explore various design considerations for MW-scale charging stations and EV battery technologies. The results show a direct correlation between optimal charging station placement and major traffic corridors such as cities with ports, e.g., Los Angeles and Oakland. Corresponding parametric sweeps reveal that while good quality of service can be achieved with a mix of 1.2-megawatt and 100-kilowatt chargers, the resultant fast charging time of 35–40 min will need higher charging power to reach parity with refueling times.

Abstract Background Novel immune checkpoint inhibitors have been often utilized for different types of malignancies as salvage therapy with varying success. One obstacle to immune checkpoint inhibitor use is the higher incidence of immune-mediated side effects that can prompt discontinuation of therapy. Remitting seronegative symmetrical synovitis with pitting edema has been described with immune checkpoint inhibitors only once previously. We report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema related to immune checkpoint inhibitor therapy and stress that these symptoms can be managed without cessation of immune checkpoint inhibitor therapy. Case presentation We present a 70-year-old white man who presented with 4 months of progressive inflammatory arthritis with pitting edema. He had been started on nivolumab therapy for his metastatic melanoma with excellent response prior to symptom onset. The symptoms started in his knees and subsequently involved both hands and feet. On evaluation, he was wheelchair bound and completely dependent for all activities of daily living. Evaluation revealed negative serological testing and plain film imaging. Ultrasound demonstrated diffuse flexor tenosynovitis and soft tissue swelling, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. He was treated with orally administered corticosteroids (0.5 mg/kg per day) which improved his symptoms significantly and allowed him to regain prior independent functioning. His corticosteroids were tapered (0.15 mg/kg per day) but not discontinued and his nivolumab treatment was not interrupted. In follow up he continued to have stable control of his melanoma as well as his remitting seronegative symmetrical synovitis with pitting edema. Conclusions In conclusion we present the first case of nivolumab-induced remitting seronegative symmetrical synovitis with pitting edema that is controlled by maintenance low-dose orally administered corticosteroids allowing for continuation of nivolumab therapy. Clinicians who encounter mild-to-moderate immune checkpoint inhibitor immune-mediated adverse effects can consider maintaining immune checkpoint inhibitor therapy with concomitant low-dose corticosteroids rather than abrupt cessation of the immune checkpoint inhibitor.

Background: The life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa. Methods: As part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use. Findings: We obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score −0·002, 95% CI −0·01 to 0·001; p=0·219) nor in South Africa (0·000, −0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individuals who had initiated ART less than 5 years previously and HIV-negative individuals in Zambia (−0·006, 95% CI −0·008 to −0·003; p

Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical theranostics. In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients, as well as future applications of recent laboratory and translational studies.Methods: Review of the literature.Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-ALA and ICG), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine can be used for rapid tumor detection and pathological tissue examination. Other emerging agents such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.Conclusion: We are standing on the doorstep of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Pneumococcal bacteriocins (pneumocins) are antibacterial toxins that mediate intra-species competition within the human host. However, the triggers of pneumocin expression are poorly understood. Using RNA-sequencing, we mapped the regulon of the pneumocin cluster (blp) of Streptococcus pneumoniae D39. Furthermore, by analogy with pneumococcal competence, we show that several antibiotics activate the blp-genes. Using real-time gene expression measurements we show that while the promoter driving expression of the two-component regulatory system blpR/H is constitutive, the remaining blp-promoters that control pneumocin expression, immunity and the inducer peptide BlpC, are pH-dependent and induced in the late exponential phase. Intriguingly, competence for genetic transformation, mediated by the paralogous ComD/E two-component quorum system, is induced by the same environmental cues. To test for interplay between these regulatory systems, we quantified the regulatory response to the addition of synthetic BlpC and competence-stimulating peptide (CSP). Supporting the idea of such interplay, we found that immediately upon addition of CSP, the blp-promoters were activated in a comD/E-dependent manner. After a delay, blp-expression was highly induced and was strictly dependent on blpRH and blpC. This raised the question of the mechanism of BlpC export, since bioinformatic analysis showed that the genes encoding the putative exporter for BlpC, blpAB, are not intact in strain D39 and most other strains. By contrast, all sequenced pneumococcal strains contain intact comAB genes, encoding the transport system for CSP. Consistent with the idea that comAB mediate BlpC export, we finally show that high-level expression of the blp-genes requires comAB. Together, our results demonstrate that regulation of pneumocin expression is intertwined with competence, explaining why certain antibiotics induce blp-expression. Antibiotic-induced pneumocin expression might therefore have unpredictable consequences on pneumococcal colonization dynamics by activating genes that mediate intra-specific interference competition.

This article traces our collective experiences as a photographer, a journalist and an academic engaged in the process of documenting the lives of South Africa's grandmothers - who are confronting the HIV/AIDS pandemic while carrying an immense history of social struggle in the apartheid era. We set out with individual aspirations to record, in visual and narrative forms, the life stories and lived experiences of members of the Grandmothers Against Poverty and AIDS (GAPA) organization based in Khayelitsha, Cape Town. Over the course of three years of building relationships and working with leaders of this organisation, we developed a social documentation project that involved a series of individual portraits, family photographs, longitudinal life narratives, organizational ethnographies and film footage. Collectively, this data formed the foundation for 'The Nevergiveups' photo exhibition at the District Six Museum and the Khayelitsha Community Centre in June 2011. This installation emerged as a collective, international effort to promote wider awareness of the significance and particularity of the juncture many South African grandmothers face - between the trauma of a collective memory of apartheid and the contemporary HIV/AIDS crisis. This project emerged in a distinct approach that combined social documentation with scholar-activism - as our professional spheres as journalist, photographer and academic sociologist intersected in a larger shared pursuit of contributing to a social documentation and activist project that would provide an archival record of South African grandmothers' lives through the elder women members of GAPA.

Transport planning relies extensively on forecasts of traveler behavior over horizons of 20 years and more. Implicit in such forecasts is the assumption that travelers’ tastes, as represented by the behavioral model parameters, are constant over time. In technical terms, this assumption is referred to as the "temporal transferability" of the models. This paper summarizes the findings from a literature review that demonstrates there is little evidence about the transferability of mode-destination models over typical forecasting horizons. The literature review shows a relative lack of empirical studies given the importance of the issue. To provide further insights and evidence, models of commuter mode-destination choice been developed from household interview data collected across the Greater Toronto and Hamilton Area in 1986, 1996, 2001, and 2006. The analysis demonstrates that improving model specification improves the transferability of the models, and in general the transferability declines as the transfer period increases. The transferability of the level-of-service parameters is higher than transferability of the cost parameters, which has important implications when considering the accuracy of forecasts for different types of policy. The transferred models over-predict the key change in mode share over the transfer period—specifically, the shift from local transit to auto driver between 1986 and 1996—but under-predict the growth in commuting tour lengths over the same period.

This special section of the Journal of Transport and Land Use focuses on location choice modeling underlying activity-travel behavior and includes five manuscripts that were originally presented in Toronto, Canada at the Thirteenth International Conference on Travel Behaviour Research, organized by the International Association for Travel Behaviour Research (IATBR).

An explanation is submitted on the concept of healthy organization, its conditioning factors and the consequences thereof. Also, a survey is made of the turbulent environmental conditions faced by organizations today, and of the complexities involved in attempts to turn the work place into a healthy environment. The author point out that nowadays jobs progressively demand a total psychological presence from individuals, which in turn calls for human relations adequate to emotionally hold people, thus constituting a basic factor in the health of organizations. Examples are included, aimed at making the contents clear.

BACKGROUND: Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer. EXPERIMENTAL DESIGN: Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis. RESULTS: Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69-0.86) and more than 10 three-marker combinations have excellent AUC values (0.91-0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p

[This paper is part of the Focused Collection on Preparing and Supporting University Physics Educators.] University educators (UEs) have a long history of teaching physics not only in formal classroom settings but also in informal outreach environments. The pedagogical practices of UEs in informal physics teaching have not been widely studied, and they may provide insight into formal practices and preparation. We investigate the interactions between UEs and children in an afterschool physics program facilitated by university physics students from the University of Colorado Boulder. In this program, physics undergraduates, graduate students, and postdoctoral researchers work with K-8 children on hands-on physics activities on a weekly basis over the course of a semester. We use an activity theoretic framework as a tool to examine situational aspects of individuals’ behavior in the complex structure of the afterschool program. Using this framework, we analyze video of UE-child interactions and identify three main pedagogical modalities that UEs display during activities: instruction, consultation, and participation modes. These modes are characterized by certain language, physical location, and objectives that establish differences in UE-child roles and division of labor. Based on this analysis, we discuss implications for promoting pedagogical strategies through purposeful curriculum development and university educator preparation.

ABSTRACT Introduction Minimally invasive surgery has recently gained interest for kidney transplantation. We aimed to describe the step-by-step technique for single-port robotic transperitoneal kidney transplantation using the SP® surgical system (Intuitive Surgical, Sunnyvale, Ca) in a pre-clinical model. Materials and Methods A male fresh cadaver model was placed in a lithotomy position. A 3cm midline incision was made 4cm cephalad to the belly button. An advanced access platform (GelPOINT, Rancho Margarita, California, USA) was inserted into the abdominal cavity through the incision. A left kidney was obtained for the local procurement organization. Bench preparation of the kidney was performed. Thereafter, the organ was introduced transperitoneal through the Alexis® wound retractor. The SP® robotic platform was docked and the pelvic fossa was targeted. The standardized steps of robotic multi-arm kidney transplant were duplicated. Primary outcomes such as intraoperative complications, rate of conversion to standard technique and operative times were recorded. Results The procedure was technically completed using the SP® robotic system without conversion or the need for additional ports. There were no intraoperative complications. The total operative time was 182 minutes, with 35 minutes spent for bench kidney. Conclusions Robotic Single-Port kidney transplantation using the SP® surgical platform is feasible in a pre-clinical model. The platform could be particularly interesting for multi-quadrant surgery such as auto-transplantation, potentially reducing the time for redocking. Further clinical studies in humans and comparison with standard surgical techniques are warranted.