Firm Creation, Firm Evolution and Clusters in Chile’s Dynamic Wine Sector: Evidence from the Colchagua and Casablanca Regions

wine, Argentina, wine cluster, regional development, Community/Rural/Urban Development, Industrial Organization, Production Economics, Q1,

Radio broadcasting and the world wide web : an exploratory study

Radio broadcasters have recently been confronted with the World Wide Web, a possible source of competition or an extension to broadcasting. Since 1994, broadcasters\u27 adoption of the Web has grown exponentially along with the growth of the Web in general. This study examines the reasons why broadcasters have adopted the Web, their perceived advantages and disadvantages of adoption, when they adopted, their plans for future use of the Web, and how they are actually using the Web. The study is divided into two parts: (1) a survey consisting of 13 Likert-type questions probing reasons for adoption and four open-ended questions probing their attitudes toward the Web and plans for its use, and (2) a content analysis of the respondents Web sites to ascertain how they actually use the Web. Data were collected from 199 respondents from during the first two months of 1997. The most cited reason for creating a station Web site was fear of losing out to competition in case the Web turns out to be successful. Promotion was the second most cited reason for establishing a Web site. Most stations had a technologically knowledgeable employee who persuaded management to establish a site. The vast majority of managers were satisfied with their site once established. However, management found that the major disadvantage of having a site is the amount of time it takes to maintain the site. This suggests that radio stations may have to add employees especially to maintain a successful site, give up on maintaining a site, or continue with an inferior site. Most stations plan to broadcast over the Web via audio streaming. Although audio streaming allows stations to broadcast content worldwide, it does not lend itself to targeting a local audience. In addition, audio streaming can create competition for radio stations because anyone with a Web server and a CD player can broadcast via audio streaming. Finally, few stations use their site to generate revenue from advertisements. Instead, they offer advertisements on the Web as value-added to on-air advertisements for their clients. Content analysis of the respondents\u27 sites indicates that few stations do enough to motivate visitors to their site. Although many stations report that they plan to enable audio streaming, at the time of this survey fewer than 15% actually utilize it. Many stations, on the other hand, include biographical information about their on-air staff. In addition, most stations include some kind of feedback mechanism such as an email address, telephone number, etc., on their site. The results have important implications for station managers. Sites need to be maintained with fresh content that motivates their audience to visit the site. Because this takes time and manpower, stations will have to either hire new staff or free current staff to work on the site

Reading on Grade Level in Third Grade: How Is It Related to High School Performance and College Enrollment?

Illustrates how third-grade reading level correlates with eighth-grade reading level, which, along with ninth-grade school traits, correlates with ninth-grade performance, which in turn correlates with high school graduation and college attendance rates

Cartografía de los mercados emergentes

El concepto de “mercados emergent es” apareci ó en la década de los años 1990 en el contexto del Nuevo Orden Mundial. Estos mercados no corresponden a áreas geográficas definidas pero corresponden a la periferia del Primer Mundo y se caracterizan por el inconmensurable potencial económico y social. Fueron activados por los capitales privados que buscaban una forma diferente a la tradicional inversión extranjera directa. Presentan diversas características por condiciones históricas, el atractivo de algunos sectores de la economía, las prioridades y percepciones de los inversionistas y por la volatilidad de las condiciones del mercado mundial

Contrasting sexual selection on males and females in a role-reversed swarming dance-fly, Rhamphomyia longicauda Loew (Diptera: Empididae)

Sex-specific ornamentation is widely known among male animals, but even among sex-role reversed species, ornamented females are rare. Although several hypotheses for this pattern exist, too few systems featuring female ornaments have been studied in detail to adequately test them. Empidine dance flies are exceptional in that many species show female ornamentation of wings, abdomens, or legs. Here we compare sexual selection in males and females of the long-tailed dance fly, Rhamphomyia longicauda Loew (Diptera: Empididae), a sex-role reversed fly in which swarming females aggregate in competition for the nuptial gifts provided by males during mating. Females in this species possess several secondary sex characters, including eversible abdominal sacs, enlarged wings, and decorated tibiae that may all function in mate attraction during swarming. Males preferentially approach large females in the swarm, but the strength and shape of selection on females and the degree to which selection is sex-specific are unknown. We estimated linear and nonlinear sexual selection on structures expressed in both male and female flies, and found contrasting patterns of sexual selection on wing length and tibia length in males and females. In females, long wings and short tibiae were associated with mating success, whereas selection on males was significantly different: males with short wings and long tibiae were most likely to mate (although tibia length was a marginally non-significant predictor of male mating success). We found no evidence for assortative or disassortative mating. Although the largest females occupied positions within the swarm closest to the entry point for choosy males, in contrast to selection for mating success these females tended to have larger tibiae than rivals. We discuss our findings in the context of the mating biology of R. longicauda compared to other empidine dance flies, and its relevance to the evolution of sexual dimorphism in general

Changing the Paradigm of Space Testing: The F.A.S.T. Program

The high cost of access to space is driven in part by a cost spiral -- higher costs lead to fewer missions which leads to a demand for higher reliability which leads to higher costs. One way to potentially break this cycle is to introduce the opportunity for rapid, low-cost experiments leading to a larger number of near term experiments which, in turn, should result in higher performance, greater reliability, and lower cost systems which will spur the demand for additional rapid, low-cost experiments. A program has been initiated to help bring this about, initially with suborbital flights and subsequently with orbital flights of small experiments and instruments. The first FAST experiment was flown on board a Scorpius SR-XM suborbital vehicle launched from White Sands Missile Range on March 9, 2001

Effect of modified vaccinia Ankara–5T4 and low-dose cyclophosphamide on antitumor immunity in metastatic colorectal cancer: A randomized clinical trial

Importance The success of immunotherapy with checkpoint inhibitors is not replicated in most cases of colorectal cancer; therefore, different strategies are urgently required. The oncofetal antigen 5T4 is expressed in more than 90% of cases of metastatic colorectal cancer (mCRC). Preliminary data using modified vaccinia Ankara–5T4 (MVA-5T4) in mCRC demonstrated that it safely induced serologic and T-cell responses. Objective To determine whether antitumor immunity in mCRC could be increased using MVA-5T4, metronomic low-dose cyclophosphamide, or a combination of both treatments. Design, Setting, and Participants In this randomized clinical trial, 55 patients with inoperable mCRC and prior stable disease after standard chemotherapy were enrolled at a single center and randomized to watch and wait (n = 9), cyclophosphamide treatment only (n = 9), MVA-5T4 only (n = 19), and a combination of MVA-5T4 and cyclophosphamide (n = 18). Patients were enrolled and treated from July 9, 2012, through February 8, 2016, and follow-up was completed on December 13, 2016. Data were analyzed based on intention to treat. Interventions Patients randomized to a cyclophosphamide group received 50 mg twice daily on treatment days 1 to 7 and 15 to 21. Patients randomized to a MVA-5T4 group received an intramuscular injection at a dose of 1 × 109 50% tissue culture infectious dose on treatment days 22, 36, 50, 64, 78, and 106. Main Outcomes and Measures The predefined primary end point was the magnitude of anti-5T4 immune responses (5T4-specific T-cell and antibody levels) generated at treatment week 7. Secondary end points included analysis of the kinetics of anti-5T4 responses, progression-free survival (PFS), and overall survival (OS). Results Fifty-two patients (38 men and 14 women; mean [SD] age, 64.2 [10.1] years) were included in the study analysis. The 5T4-specific antibody immune responses were significantly increased in the MVA-5T4 (83.41 [36.09] relative units [RU]; P = .02) and combination treatment (65.81 [16.68] RU; P = .002) groups compared with no treatment (20.09 [7.20] RU). Cyclophosphamide depleted regulatory T cells in 24 of 27 patients receiving MVA-5T4, independently prolonging PFS (5.0 vs 2.5 months; hazard ratio [HR], 0.48; 95% CI, 0.21-1.11; P = .09). MVA-5T4 doubled baseline anti-5T4 responses in 16 of 35 patients, resulting in significantly prolonged PFS (5.6 vs 2.4 months; HR, 0.21; 95% CI, 0.09-0.47; P < .001) and OS (20.0 vs 10.3 months; HR, 0.32; 95% CI, 0.14-0.74; P = .008). No grade 3 or 4 adverse events were observed. Conclusions and Relevance This initial randomized clinical immunotherapy study demonstrates a significant survival benefit in mCRC. Prior depletion of regulatory T cells by cyclophosphamide did not increase immune responses generated by MVA-5T4 vaccination; however, cyclophosphamide and MVA-5T4 each independently induced beneficial antitumor immune responses, resulting in prolonged survival without toxic effects. Larger clinical trials are planned to further validate these data

Genetic diversity and phylogenetic analysis of the native mountain ponies of Britain and Ireland reveal a novel rare population

The conservation of unique populations of animals is critical in order to preserve valuable genetic diversity and, where populations are free-living, maintain their irreplaceable influence upon habitat ecology. An accurate assessment of genetic diversity and structure within and between populations is crucial in order to design and implement conservation strategies in natural and domesticated species. Moreover, where it is possible to identify relic populations that are related to a structured breed an ideal opportunity presents itself to model processes that reveal historical factors that have shaped genetic diversity. The origins of native UK mountain and moorland ponies are uncertain, but they may have directly descended from prehistoric populations and potentially harbour specific adaptations to the uplands of Britain and Ireland. To date, there have been no studies of population structure and genetic diversity present within a free-living group of ponies in the Carneddau mountain range of North Wales. Herein, we describe the use of microsatellites and SNPs together with analysis of the mitochondrial control region to quantify the extent and magnitude of genetic diversity present in the feral Carneddau pony and relate this to several recognised British and Irish pony breeds. Our results establish that the feral Carneddau ponies represent a unique and distinctive population that merits recognition as a defined population and conservation priority. We discuss the implications for conservation of this population as a unique pool of genetic diversity adapted to the British uplands and potentially of particular value in maintaining the biodiversity of these habitats

Low-dose cyclophosphamide induces anti-tumor T-cell responses which associate with survival in metastatic colorectal cancer

Purpose: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. Experimental Design: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not. The absolute number, phenotype and anti-tumor function of peripheral blood-derived lymphocyte subsets were monitored throughout treatment, along with 18-month follow-up. Results: Initially CPM reduced proliferation in all lymphocyte subsets, however, a rapid mobilization of effector T-cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell and NK-cell numbers occurred. The expansion and subsequent activation of effector T-cells was focused on tumor-specific T-cells, producing both granzyme B and IFN-gamma. CPM-treated patients demonstrating the most enhanced IFN-gamma+ tumor-specific T-cell responses exhibited a significant delay in tumor progression (HR=0.29, 95% CI 0.12-0.69, P=0.0047), compared to non-responders and no-treatment controls. Conclusions: CPM-induced Treg-depletion is mirrored by a striking boost to anti-tumor immunity. This study provides the first direct evidence of the benefit of naturally primed T-cells in mCRC patients. Our results also support the concept that non-mutated self-antigens can act as useful targets for immunotherapies

MVA-5T4 immunotherapy and low-dose cyclophosphamide for advanced colorectal cancer (TaCTiCC): An open-label, randomized phase I/II trial.

Background: Current immunotherapies including checkpoint inhibitors and vaccines for advanced colorectal cancer (CRC) have been largely ineffective. We hypothesized that combining an MVA-based vaccine targeting the tumor-associated antigen 5T4 (TroVax) with low-dose cyclophosphamide to deplete Foxp3+regulatory T-cells (Tregs), could improve immunological responses and patient outcomes. Methods: In this open-label phase I/II clinical trial, TaCTiCC (TroVax and Cyclophosphamide Treatment in Colorectal Cancer) 53 patients with inoperable metastatic CRC were randomized to receive either no treatment (group 1, n=8), metronomic low-dose CPM (50mg B.D. during treatment weeks 1&3; group 2, n=9), TroVax only (6 i.m. injections weeks 4 to 16, group 3, n=18), or low-dose CPM followed by TroVax (group 4, n=18). The primary endpoint was boosted anti-5T4 responses at week 7, as measured by increased T-cell and antibody responses; secondary endpoints included progression-free (PFS)/overall survival (OS), and anti-5T4 responses over the trial period. Results: CPM depleted Tregs in 21/27 patients during treatment week 3 (p=0.0045), resulting in significantly prolonged PFS amongst groups 2&4 over group 1 (5.0 vs. 2.5 months, HR=0.17 95% CI 0.048-0.62, p=0.0072). TroVax induced a >2-fold increase in anti-5T4 immune responses in 15/36 group 3&4 patients; these patients experienced significantly prolonged median PFS (6.5 vs. 2.4 months, HR 0.31 95% CI 0.14-0.65, p=0.0022) and OS (20 vs. 12 months, HR=0.37 95% CI 0.17-0.82, p=0.014). Combination of CPM & TroVax was not significantly superior. The primary endpoint at a single timepoint was not met since CPM-induced responses declined by week 7, and TroVax-induced responses were greatest at weeks 10-16. No serious adverse events were reported. Conclusions: Both CPM and TroVax induced highly beneficial anti-tumor immune responses resulting in significantly prolonged survival of end-stage CRC patients without toxicity. This is the first study to show a clear benefit of immunotherapy in advanced CRC, and suggests this approach may be superior (and less toxic) to continuous palliative chemotherapy in these patients