Developing a methodology for ex post evaluation of the wider impact of the restoration of rail services to previously disconnected or isolated regions on employment and property prices and accessibility to jobs and essential services.

As well as improving access to jobs and essential services, the re-establishment of rail links to larger, more remote areas may produce wider economic and social impacts both within the region and beyond. Recent developments have highlighted the need for improved ex post evaluation of such impacts, particularly in formerly disconnected or isolated regions. The main thrust of this research was through investigating ex post situations both spatially and temporally to determine cause-effect relationships. This required developing a methodological approach which would match those objectives and adapted pre-existing methods to develop a methodology for appraisal particularly relevant to remote, rural or disconnected regions. Using three case studies - the Robin Hood line (1998), the Stirling-Alloa line (2008), and Borders Rail (2015) as representing different stages of recent rail investment in previously disconnected regions, and applying mainly secondary data sources, a counterfactual was developed which allowed a meaningful comparison between areas subject to treatment i.e. rail intervention, and those not treated i.e. either unaffected or minimally affected by the intervention and to establish any differences between findings in urban studies. Treatment groups were based on distance thresholds where the control group was selected from remaining locations in the region. There appeared to be some benefit in application of clustering and propensity matching to effect a more balanced comparison between similar locations in the treatment and control groups. An important consideration was the accessibility characteristic which conventionally has been distance to the nearest rail station. However, two additional measures were utilised here: a distance to station ratio (which measured the percentage improvement in distance to station following the rail intervention) and a job accessibility index which assessed the improvement in access to jobs based on skills matching and the cost of commuting. The job accessibility index was developed to take into account the limitations in travel in more remote communities where services are less frequent and commuting distances often greater than in the urban situation. The cost of travel was recognised as a key factor affecting accessibility and generalised cost allowed the cost of commuting to be calculated using local values of speed and cost of transport. Job accessibility was based on comparing the percentage skills share at each location, matched to actual jobs at all neighbouring destination locations. The job accessibility index allowed a measure of accessibility based on the original job market, but could also be used to assess the effect on accessibility of a slump in employment by considering the current job market. Without job skills matching, job accessibility appeared to be overestimated as the seemingly high attraction of job opportunities may not always synchronise with the skills set in that location. It yielded good results when used as an accessibility characteristic in the hedonic models, being a more complex measure than distance from rail station as it encompassed the whole regional employment picture relative to each location. Previous research had suggested some correspondence between rail access improvements and increased property price and employment levels. Four different approaches were examined here to assess causality: a descriptive comparison approach, a DID (difference-in-difference) model, a fixed effects hedonic model and a GWR (Geographically Weighted Regression) model. These incorporated other factors such as changes in local and property characteristics over the period spanning each intervention. The descriptive approach looked at individual variables in isolation pre- and post- intervention broken into treatment and control to assess any impacts but ignored the combined effect of other explanatory factors. The output indicated a discernible effect of treatment in some cases, and was useful in corroborating variables to carry forward to the model. For property impacts, the difference-in-difference approach produced contrasting findings for the case study regions. For job impacts, there was a positive effect on employment density of being closer to a rail station and of improvement in job accessibility, but for Borders Rail this was not statistically significant which may be due to the limited amount of data available at this stage. The fixed effects model showed that for property impacts the distance to rail station and distance ratio and improvement in job accessibility were all significant factors. A modified spatial-temporal version of Geographically Weighted Regression estimated local parameters through time by examining changes in coefficients for two separate years spanning the intervention for each case study. The property model showed variation across each region in the negative relationship between price and distance to the nearest station for both the established case study regions. For the jobs model, the relationship between employment density and distance to the nearest station showed that the distance from the rail network was critical in terms of the job market. The findings suggest some causality linking rail investment to house price changes and employment density, dependent on the scale of the rail intervention and the regional context. Improvements in rail transport infrastructure could produce economic benefits affected by the proximity to new stations and relate to the effect on property prices. Although improved job accessibility allowing increased commuting, spatial, temporal and economic barriers may still prevent more economically vulnerable neighbourhoods within each region from receiving the full benefit of the intervention. In conclusion, there are implications for practice in terms of making a case for new rail infrastructure, application in a WebTag style appraisal or evaluation, and new information on spatial patterns of employment and property prices. In addition, consideration is given to expansion of the methodology to other types of transport intervention as well as application in an urban context

Preserving spatial and temporal dimensions in observational data of segregation

Recent approaches to the study of intergroup contact have emphasised the need for naturalistic studies and the importance of paying attention to the spatiality of contact. In this article it is argued that it is important to preserve both spatiality and temporality when studying inter-group contact in naturalistic settings. This is not easy to do with existing observational methods, and a novel approach is proposed. Photographs are taken of a public space with a fixed periodicity and vantage point, and with knowledge of the physical layout of the space, three-dimensional, time-marked data points are recorded for each inhabitant. A public space on a university campus was used as a test bed, and data are reported that show it to be very useful, giving fresh insights into the nature of segregation and integration in informal leisure spaces, as well as providing evidence of the importance of taking temporality into account when studying naturalistic instances of inter-group contact

Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS)

A remotely piloted aircraft research facility is described that will provide new capabilities for atmospheric and oceanographic measurements. The aircraft can fly up to 24 h over remote ocean regions, at low or high altitude, and in various other challenging mission scenarios. The aircraft will fly research missions at speeds of 40 m s^(−1) and provide high spatial resolution measurements. Data will be transmitted in real time to a ground station for analysis and decision-making purposes. The facility will expand the opportunities for universities to participate in field measurement programs

Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC Study

BackgroundThe addition of cetuximab to perioperative chemotherapy for operable colorectal liver metastases resulted in a shorter progression free survival. Details of disease progression are described to further inform the primary study outcome.MethodsA total of 257 KRAS wild-type patients were randomised to chemotherapy alone or chemotherapy with cetuximab. Data regarding sites and treatment of progressive disease were obtained for the 109 (chemotherapy n=48, chemotherapy and cetuximab n=61) patients with progressive disease at the cut-off date for analysis of November 2012. ResultsThe liver was the most frequent site of progression (chemotherapy 67% (32/48); chemotherapy and cetuximab 66% (40/61)). A higher proportion of patients in the cetuximab group had multi-site/other sites of progressive disease (chemotherapy 8%, 4/48; chemotherapy and cetuximab 23%, 14/61 p=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further chemotherapy, most frequently irinotecan based. Twenty two patients, 11 in each arm, received cetuximab as a further line agent. ConclusionBoth the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery. <br/

Evidence-based guidelines for managing patients with primary ER+ HER2− breast cancer deferred from surgery due to the COVID-19 pandemic

Many patients with ER+ HER2- primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensitive tumors and should be prioritised for early surgery or neoadjuvant chemotherapy rather than NeoET during or in the aftermath of the COVID-19 pandemic for safety or when surgical activity needs to be prioritized. For postmenopausal patients, our data provide strong support for the use of ER and PgR status at diagnosis for triaging of patients into three groups in which (taking into account clinical factors): (i) NeoET is likely to be inappropriate (Allred ER 10%) indicates a higher priority for early surgery. Too few data were available for premenopausal patients to provide a similar treatment algorithm. These guidelines should be helpful for managing patients with early ER+ HER2- breast cancer during and in the aftermath of the COVID-19 crisis

Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae

Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3–4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role

Interdisciplinary perspectives on multimorbidity in Africa: Developing an expanded conceptual model

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, setting, and participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main outcomes and measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined

1954: Abilene Christian College Bible Lectures - Full Text

Preface The 1954 Abilene Christian College Lectureship was one of the best attended and most successful in the history of the school. Considerable interest was manifested in the timely theme, “Overcoming Dangerous Tendencies,” and in the two special topics, “Ways and Means of Doing Mission Work,” and “Caring For Widows and Orphans.” The reports from the mission fields were highly stimulating, and all in all, the speeches were unusually high caliber. The Panel Discussions were also on timely subjects and well presented. They received a warm response, as did also the thirty classes that were conducted each day. These classes were taught by persons expert in their particular fields, and covered a wide range of interests to the faithful, working Christian. We at Abilene Christian College predict for this book of Lectures a wide and hearty reception, and believe that its reading will issue in profit to the individual and to the church at large. J. D. Thomas Lectureship Directo