International Entrepreneuship and Geographic Location: An Empirical Examination of New Venture Internationalization

In this paper, we argue that geographic location may be one reason why some ventures are able to acquire the resources needed to internationalize while others cannot. We use ecological arguments to predict an inverted U-shaped relationship between the concentration of industry clustering within a geographic location and the venture\u27s internationalization. We also explore whether venture characteristics influence the nature of this relationship. Our hypotheses are regressed on international intensity and scope, and analyzed through a sample of 156 publicly held new ventures. Results confirm that location influences new venture internationalization, and firm characteristics impact the nature of the relationship

Entrepreneurial Orientation and International Scope: The Differential Roles of Innovativeness, Proactiveness, and Risk-Taking

This research integrates the international business and entrepreneurship literatures by examining the independent influences of innovativeness, proactiveness, and risk-taking on the ability of a firm to broaden its scope across international markets. For each dimension of entrepreneurial orientation, a cost–benefit framework is applied to highlight the trade-offs associated with different levels in the internationalization context. Based on a unique dataset of 500 SMEs spanning 10 industries, the results reflect the consequences of being “stuck in the middle” with respect to their strategic posture on innovativeness and proactiveness, but reveal a nuanced role for risk-taking behavior. The non-uniform and non-linear relationships from the findings contribute to a better understanding of when the individual dimensions of entrepreneurial orientation help or hinder entrepreneurial firms in the internationalization process

Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?

Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock

Økologisk mjølkeproduksjon uten kraftfôr

Det er økende interesse hos forbrukere for mjølk og mjølkeprodukt som er produsert uten bruk av kraftfôr med bare beite og konservert gras i fôrrasjonen. Rørosmeieriet AS, som foredler økologisk produsert mjølk, er interessert i å etablere egen produksjonslinje for mjølkeprodukt fra kyr produsert uten kraftfôr. For mjølkeprodusenten kan det å kutte ut kraftfôr i fôrrasjonen få store konsekvenser for mjølkeytelse og dermed økonomi. Formålet med dette arbeidet var å vurdere hva en kan forvente seg av mjølkeytelse og mjølkekvalitet ved å kutte ut kraftfôr i rasjonen. Helse og fruktbarhet hos dyra, næringsstofforsyning til gården og totaløkonomien vil sannsynligvis også påvirkes, og det var et mål å beregne hva mjølkeprodusenten må ha i merpris for mjølka for å opprettholde dekningsbidraget. Arbeidet er gjennomført som en litteraturstudie og som en egen analyse der vi brukte data fra fire økologiske mjølkeproduksjonsbruk i Rørosområdet, som leverer mjølk til Rørosmeieriet. For de fire bruka gjorde vi en scenarioanalyse der vi estimerte mjølkeproduksjon og fôrforbruk uten kraftfôr i beitetida, men med kraftfôr i innefôringstida, og helt uten kraftfôr i rasjonene. Data generert fra scenarioanalysen blei sammenlignet med dagens tilstand med hensyn på mjølkeytelse, næringsstoff-balanse og økonomi. Vi tok også ut mjølkeprøver fra tanken før beiteslipp og i beitetida for å analysere kvaliteten av mjølk. Det er i norske forsøk funnet gjennomsnittlig mjølkeytelse på mellom 3000 og 5000 kg mjølk per ku og laktasjon uten kraftfôr. Scenarioanalysen viste at produksjonen helt uten kraftfôr er om lag 5500-6500 kg, mellom 22 og 26% lavere enn fôring opp mot produksjonspotensialet, og mellom 12 og 16% lavere dersom en gir kraftfôr i innefôringstida og ingen kraftfôr i beitetida. Totalt grovfôropptak vil være 19-27% høyere uten kraftfôr sammenlignet med fôring med kraftfôr. Litteraturanalysen viste at uten kraftfôr i rasjonen vil konsentrasjonen av fett og protein i mjølk reduseres, men andelen av ernæringsmessige gunstige fettsyrer (f.eks. C18:3n-3, og CLA) øker. Beiting har særlig positiv effekt på andelen av ernæringsmessige gunstige fettsyrer og reduserer samtidig de som regnes som ugunstige (f.eks. C14:0, C16:0). Videre så øker innholdet av E vitamin i mjølka på beite sammenlignet med innefôring. Analyse av tankmjølka fra de fire bruka viste stor variasjon i mjølkekvalitet, som sannsynligvis skyldes ulik fôring. Men det er tydelig effekt av beiting på fettsyresammensetning (redusert andel C16:0 og økt andel C18:3n-3). Det er tydelig at mjølkefettet produsert på beite var mykere enn mjølkefett fra innefôringsperioden. Høstkalving og negativ energibalanse tidlig i laktasjonen kan gi dårlig fruktbarhet, og det er lettere å få til produksjon uten kraftfôr med konsentrert vårkavling. Lavere ytelse reduserer risikoen for enkelte produksjonssykdommer, men samtidig har bonden færre muligheter til å justere inntak av energi, protein og mineraler for å oppnå en balansert diett. Ketose kan bli en utfordring når kraftfôrandelen reduseres eller hvis kraftfôret kuttes helt ut. Moderat hold i sinperioden forebygger flere produksjons-relaterte sjukdommer. Det er svært viktig å følge opp med tilskudd av mineraler og vitaminer i rasjoner uten kraftfôr, siden dette ofte er tilsatt kraftfôret. Videre er det viktig å ha energirikt grovfôr i starten av laktasjonen, og en må ha økt fokus på grovfôrkvalitet og ta regelmessige grovfôranalyser. Import av husdyrgjødsel er en viktig kilde for nitrogen (N), fosfor (P) og kalium (K), og bidrar til at på de fleste gårdene er det et lite overskudd av disse næringsstoffene i dag. Scenarionalysen viste at for alle gårdene ble næringsstoffbalansen av N, P og K lavere sammenlignet med dagens drift når kraftfôr helt eller delvis ble kuttet ut. For gårdene som ikke importerer husdyrgjødsel, blir næringsstoffbalansen så vidt positiv for N og omtrent i balanse for P og K. Dersom det ikke kjøpes inn noe kraftfôr, er det tendenser til negativ næringsstoffbalanse. Det blir viktig å følge utviklingen i næringsinnholdet i jorda hvis kraftfôrinnkjøpet reduseres eller kuttes ut. Den økonomiske analysen viste at mjølkeleveransene blir redusert sammenlignet med dagnes drift når kraftfôr helt eller delvis blir kuttet ut. For tre av de fire bruka vil det gjøre at dekningsbidraget reduseres, mens det for det siste opprettholdes. For at dekningsbidraget skal opprettholdes på dagnes nivå, må merprisen på mjølk være 0 - 0,84 kr/liter der kraftfôr kuttes i beitetida, og 0 – 1,94 kr/liter dersom kraftfôr kuttes helt ut. Årsaken til den store variasjonen i behovet for merpris, skyldes i all hovedsak variasjon i arealgrunnlag. For bruk som har stort areal eller lav kraftfôrtildeling i dag kan en overgang til drift med lite eller ikke noe kraftfôr være mulig uten store økonomiske konsekvenser. Vi konkluderer med at dersom det er ønske om mjølk med høy ernæringsmessig kvalitet, så vil det beste være å bare unngå kraftfôr i beitetida. Beiting uten tilskudd med kraftfôr er lettere å få til enn total kraftfôrfri fôring med hensyn til helse og fruktbarhet hos kyrne og økonomi, samtidig som mjølkekvaliteten på beite i stor grad vil være det samme om kua får kraftfôr i innefôringstida før beite eller ikke. Det er viktig å undersøke om en slik tilnærming er akseptabel for forbrukere som ønsker å kjøpe «grasfôra mjølk» til en merpris

Spectral analysis of the AMXP IGR J17591-2342 during its 2018 outburst

The Accreting Millisecond X-ray Pulsar IGR J17591-2342 is a LMXB system that went in outburst on August 2018 and it was monitored by the NICER observatory and partially by other facilities. We aim to study how the spectral emission of this source evolved during the outburst, by exploiting the whole X-ray data repository of simultaneous observations. The continuum emission of the combined broad-band spectra is on average well described by an absorbed Comptonisation component scattering black-body-distributed photons peaking at (0.8+/-0.5) keV, by a moderately optically thick corona (tau=2.3+/-0.5) with temperature of (34+/-9) keV. A black-body component with temperature and radial size of (0.8+/-0.2) keV and (3.3+/-1.5) km respectively is required by some of the spectra and suggests that part of the central emission, possibly a fraction of the neutron star surface, is not efficiently scattered by the corona. The continuum at low energies is characterised by significant residuals suggesting the presence of an absorption edge of O VIII and of emission lines of Ne IX ions. Moreover, broad Fe I and Fe XXV K-alpha emission lines are detected at different times of the outburst, suggesting the presence of reflection in the system.Comment: 13 pages, 7 figures, accepted for publication on MNRA

Expansion of Thaumarchaeota habitat range is correlated with horizontal transfer of ATPase operons.

Thaumarchaeota are responsible for a significant fraction of ammonia oxidation in the oceans and in soils that range from alkaline to acidic. However, the adaptive mechanisms underpinning their habitat expansion remain poorly understood. Here we show that expansion into acidic soils and the high pressures of the hadopelagic zone of the oceans is tightly linked to the acquisition of a variant of the energy-yielding ATPases via horizontal transfer. Whereas the ATPase genealogy of neutrophilic Thaumarchaeota is congruent with their organismal genealogy inferred from concatenated conserved proteins, a common clade of V-type ATPases unites phylogenetically distinct clades of acidophilic/acid-tolerant and piezophilic/piezotolerant species. A presumptive function of pumping cytoplasmic protons at low pH is consistent with the experimentally observed increased expression of the V-ATPase in an acid-tolerant thaumarchaeote at low pH. Consistently, heterologous expression of the thaumarchaeotal V-ATPase significantly increased the growth rate of E. coli at low pH. Its adaptive significance to growth in ocean trenches may relate to pressure-related changes in membrane structure in which this complex molecular machine must function. Together, our findings reveal that the habitat expansion of Thaumarchaeota is tightly correlated with extensive horizontal transfer of atp operons

Hβ\beta spectroscopy of the high-inclination black hole transient Swift J1357.2-0933 during quiescence

Swift J1357.2-0933 is a transient low-mass X-ray binary hosting a stellar-mass black hole. The source exhibits optical dips and very broad emission lines during both outburst and quiescence, which are thought to be the result of a high orbital inclination. We present phase-resolved spectroscopy obtained with the 10.4m Gran Telescopio Canarias (GTC). The spectra focus on the $\rm{H}\beta$ spectral region during X-ray quiescence. The emission line is exceptionally broad (full width at half maximum, FWHM > 4000 \AA), in agreement with previous studies focused on $\rm{H}\alpha$. A two-Gaussian fit to the prominent double-peaked profile reveals a periodic variability in the centroid position of the line. We also produced a diagnostic diagram aimed at constraining additional orbital parameters. Together, they allow us to independently confirm the orbital period of the system using a new dataset obtained five years after the previous outburst. However, our estimates for both the systemic velocity and the radial velocity semi-amplitude of the black hole reveal larger values than those found in previous studies. We argue that this could be explained by the precession of the disc and the presence of a hotspot. We found evidence of a narrow inner core in the double-peaked H$\beta$ emission profile. We studied its evolution across the orbit, finding that it is likely to result from the occultation of inner material by the outer rim bulge, further supporting the high orbital inclination hypothesis.Comment: 6 pages, 4 figure

The accretion/ejection link in the neutron star X-ray binary 4U 1820-30 I: A boundary layer-jet coupling?

The accretion flow / jet correlation in neutron star (NS) low-mass X-ray binaries (LMXBs) is far less understood when compared to black hole (BH) LMXBs. In this paper we will present the results of a dense multi-wavelength observational campaign on the NS LMXB 4U 1820-30, including X-ray (Nicer, NuSTAR and AstroSAT) and quasi-simultaneous radio (ATCA) observations in 2022. 4U 1820-30 shows a peculiar 170 day super-orbital accretion modulation, during which the system evolves between "modes" of high and low X-ray flux. During our monitoring, the source did not show any transition to a full hard state. X-ray spectra were well described using a disc blackbody, a Comptonisation spectrum along with a Fe K emission line at 6.6 keV. Our results show that the observed X-ray flux modulation is almost entirely produced by changes in the size of the region providing seed photons for the Comptonisation spectrum. This region is large (about 15 km) in the high mode and likely coincides with the whole boundary layer, while it shrinks significantly (<10 km) in low mode. The electron temperature of the corona and the observed RMS variability in the hard X-rays also exhibit a slight increase in low mode. As the source moves from high to low mode, the radio emission due to the jet becomes about 5 fainter. These radio changes appear not to be strongly connected to the hard-to-soft transitions as in BH systems, while they seem to be connected mostly to variations observed in the boundary layer.Comment: 12 pages, 6 figures. Accepted for publication by MNRA

Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial

Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the PARP inhibitor olaparib significantly improves progression-free survival versus placebo. We assessed the effect of maintenance olaparib on overall survival in patients with platinum-sensitive recurrent serous ovarian cancer, including those with BRCA1 and BRCA2 mutations (BRCAm). / Methods: In this randomised, placebo-controlled, double-blind, phase 2 trial involving 82 sites across 16 countries, patients with platinum-sensitive recurrent serous ovarian cancer who had received two or more courses of platinum-based chemotherapy and had responded to their latest regimen were randomly assigned (1:1) using a computer-generated sequence to receive oral maintenance olaparib (as capsules; 400 mg twice a day) or a matching placebo by an interactive voice response system. Patients were stratified by ancestry, time to progression on penultimate platinum, and response to most recent platinum. Patients and investigators were masked to treatment assignment by the use of unique identifiers generated during randomisation. The primary endpoint of the trial was progression-free survival. In this updated analysis, we present data for overall survival, a secondary endpoint, from the third data analysis after more than 5 years’ follow-up (intention-to-treat population). We did the updated overall survival analysis, described in this Article at 77% data maturity, using a two-sided α of 0·95%. As the study was not powered to assess overall survival, this analysis should be regarded as descriptive and the p values are nominal. We analysed randomly assigned patients for overall survival and all patients who received at least one dose of treatment for safety. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT00753545. / Findings: Between Aug 28, 2008, and Feb 9, 2010, 265 patients were randomly assigned to olaparib (n=136) or placebo (n=129). 136 patients had deleterious BRCAm. The data cutoff for this analysis was Sept 30, 2015. An overall survival advantage was seen with maintenance olaparib versus placebo in all patients (hazard ratio [HR] 0·73 [95% CI 0·55–0·96]; nominal p=0·025, which did not meet the required threshold for statistical significance [p<0·0095]; median overall survival was 29·8 months [95% CI 26·9–35·7] for those treated with olaparib vs 27·8 months [24·9–33·7] for those treated with placebo), and in patients with BRCAm (HR 0·62 [95% CI 0·41–0·94] nominal p=0·025; 34·9 months [95% CI 29·2–54·6] vs 30·2 months [23·1–40·7]). The overall survival data in patients with BRCA wild-type were HR 0·83 (95% CI 0·55–1·24, nominal p=0·37; 24·5 months [19·8–35·0] for those treated with olaparib vs 26·6 months [23·1–32·5] for those treated with placebo). 11 (15%) of 74 patients with BRCAm received maintenance olaparib for 5 years or more. Overall, common grade 3 or worse adverse events in the olaparib and placebo groups were fatigue (11 [8%] of 136 patients vs four [3%] of 128) and anaemia (eight [6%] vs one [1%]). 30 (22%) of 136 patients in the olaparib group and 11 (9%) of 128 patients in the placebo group reported serious adverse events. In patients treated for 2 years or more, adverse events in the olaparib and placebo groups included low-grade nausea (24 [75%] of 32 patients vs two [40%] of five), fatigue (18 [56%] of 32 vs two [40%] of five), vomiting (12 [38%] of 32 vs zero), and anaemia (eight [25%] of 32 vs one [20%] of five); generally, events were initially reported during the first 2 years of treatment. / Interpretation: Despite not reaching statistical significance, patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy after platinum-based chemotherapy appeared to have longer overall survival, supporting the reported progression-free survival benefit. Clinically useful long-term exposure to olaparib was seen with no new safety signals. Taken together, these data support both the long-term clinical benefit and tolerability of maintenance olaparib in patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer. / Funding: AstraZeneca