Technology-Based Competitive Advantages of Young Entrepreneurial Firms: Conceptual Development and Empirical Exploration

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordWe explore the factors that contribute to the technological distinctiveness of young entrepreneurial firms. We claim that a young firm's technological distinctiveness is partly the result of entrepreneurs and their orientations toward uncertainty. In certain locations, however, young firms have more means to invest in their technology base. We integrate these two perspectives together, and provide an original explanation and understanding of the technological distinctiveness of young entrepreneurial firms. Our empirical observations among Finnish firms give support to our main hypotheses and therefore highlight the factors that contribute to technology-based competitive advantage of young firms.Finnish Funding Agency for Technology and Innovation (TEKES

Survival and growth patterns among new technology-based firms: Empirical study of cohort 2006 in Sweden

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThis study investigates the survival and growth trends in a cohort of new technology‐based firms (NTBFs) established in Sweden in 2006. This cohort has faced both an economic upswing and a severe downturn, which started in 2008, and by 2014 provides 8 years of historical records. Our study makes several contributions to the current understanding of NTBF survival and growth. First, our empirical observations show that many NTBFs (72 percent) from the 2006 cohort were still operating at the end of 2014, indicating a much higher survival rate than those found in previous studies. Second, surviving firms from the 2006 cohort positively affected employment, as their annual job creation was higher than the reduction in employment caused by exiting firms. Third, very few companies experienced high‐growth during their first 7 years, and employment growth and sales growth were highly correlated among high‐growth firms

What is the effect of MRI with targeted biopsies on the rate of patients discontinuing active surveillance? A reflection of the use of MRI in the PRIAS study

Background The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. Methods Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. Results In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. Conclusions Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted.Peer reviewe

Mobilising finance and achieving early growth in new technology-based firms: a legitimacy perspective

This is the author accepted manuscript. The final version is available from Emerald via the DOI in this recordPurpose This study investigates a mediational model between legitimated elements, financial resource mobilisation and subsequent early firm growth among New Technology-Based Firms (NTBFs) using conformity and control perspectives of legitimacy. Design/methodology/approach To test the hypotheses, a longitudinal database of 303 NTBFs from Sweden, Finland and France is used. The ordinary least square regression analysis method is applied, and the proposed mediation relationships are studied by employing the four-step approach developed by Baron and Kenny (1986). Findings This study finds that based on the conformity principle, two out of three legitimated elements (business plan and incubator relationship, but not start-up experience) have an impact on financial resource mobilisation, which in turn, is associated with early growth in NTBFs based on the control principle. Thus, financial resource mobilisation positively mediates the relationships among the two legitimated elements and early growth in NTBFs. Research limitations/implications This study has several limitations, which also generate promising pathways for future research. Future research should study the relationship between the three legitimacy elements and financial resource mobilisation and early growth across a wider range of firms and settings. The questionnaire was also based on a single point in time and could not capture the evolving nature of the legitimacy elements and fundraising. Hence, future research can examine the multidimensionality of these processes; longitudinal qualitative studies can be a complement, allowing for a better understanding of the impact of legitimacy on NTBFs. Practical implications The findings offer implications for managers of NTBFs because developing legitimacy is critical to NTBFs early growth and development. The findings indicate that NTBFs' founders must systematically develop business plans and that incubators help enhance legitimacy through a signalling. Social implications It is believed that the study meaningfully contributes to the collective understanding of the role of legitimacy in driving the development of NTBFs. Given the importance of NTBFs in our economies, coupled with the lack of attention given to the role of mobilisation of external resources in explaining NTBF early growth, it is believed that the study is both timely and important. Originality/value The findings meaningfully contribute to the collective understanding of NTBF growth. While there are studies that have examined the antecedents of growth and finance separately, this study proposes a novel mediational model that integrates both and tests it empirically.Peter Wallenberg Foundation for Economics and Technolog

Ethical issues in the care of patients with stroke: A scoping review

Aims and objectives: The aim was to identify and analyse the ethical issues in the care of patients with stroke (PwS). The goal was to understand the nature of the existing knowledge on the topic and to identify whether there are ethical issues specific to the care of PwS. Background: Stroke is a disease with possible multiple effects on the patient's overall condition and experienced ethical issues in the care. Additionally, stroke impacts the life of the significant other. For health professionals, the care of PwS is challenging at different stages of the care process. The care of stroke includes several ethically sensitive situations from the perspectives of all participants. Design: Scoping review. Methods: The review was conducted following the five-stage methodological framework of Arksey and O'Malley (2005). The literature search was conducted in several electronic databases and complemented with a manual search, resulting in 15 reviewed articles. The analysis was conducted by charting descriptive numerical data and by content analysis of the narrative representations. Results: The studies focused on hospital or rehabilitation contexts and a high number of studies had a qualitative approach. Three main themes were identifiable: “decision-making as an ethically challenging act,” “care process-specific ethical issues” and “environmental ethical issues.”. Conclusions: Ethical issues occur at different stages of the care process of PwS and from the viewpoints of all those involved. However, not all the recognised ethical issues were stroke specific. As the number of the reviewed articles was limited, more research is needed for a comprehensive understanding of the topic. Relevance to clinical practice: Individual health professionals may use the results in observing their own action from an ethical perspective and to deepen the ethical understanding of the care of PwS. In health care organisations, the results may be used in developing the ethical quality of care.</p

A distinct M2 macrophage infiltrate and transcriptomic profile decisively influence adipocyte differentiation in lipedema

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.Peer reviewe

Short duration of upper extremity lymphedema correlates with a favorable cytokine response after lymph node transfer surgery

Vascularized lymph node transfer surgery (VLNT) can provide benefit to lymphedema patients. Cytokines mayplaya role in the development oflymphedema and in the regeneration oflymphatic vessels after VLNT. Ourprimary aim was to investigate whether the VLNTpatients have a specific cytokine profile. Our secondary aim was to see whether the preoperative lymphedema or severity affects the postoperative cytokine response. Wound exudate was gathered from 18 patients undergoing VLNT on the first and sixth postoperative day (POD). The concentrations of IL-10, TNF-alpha, TGF-beta 1 and VEGF-C were analyzed using enzyme-inked immune-sorbent assays. A general score was generated to assess the benefit ofthe surgery. The changes in cytokine concentrations (1(st) POD-6th POD) were correlated with the pre- andpostoperative lymphedema related factors. A shorter duration oflymphedema preoperatively correlated with an increase in the concentration of IL-10 and TNF-beta during the first six PODs (IL-10: r=0.495, p=0.051; TNF-alpha: p=0.006) and a decrease in the concentration of 7VF-111 (r= p=0.020). The increase ofthe concentration of TNF-alpha during the first six PODs also correlated with a greater total general score (r=0.775, p=0.005) and hence indicated a better response to the surgery. The patients with a shorter duration oflymphedema preoperatively had a more favorable cytokine response during the first six PODs after VLNT

A Multivariable Approach Using Magnetic Resonance Imaging to Avoid a Protocol-based Prostate Biopsy in Men on Active Surveillance for Prostate Cancer-Data from the International Multicenter Prospective PRIAS Study

Publisher Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.BACKGROUND: There is ongoing discussion whether a multivariable approach including magnetic resonance imaging (MRI) can safely prevent unnecessary protocol-advised repeat biopsy during active surveillance (AS). OBJECTIVE: To determine predictors for grade group (GG) reclassification in patients undergoing an MRI-informed prostate biopsy (MRI-Bx) during AS and to evaluate whether a confirmatory biopsy can be omitted in patients diagnosed with upfront MRI. DESIGN, SETTING, AND PARTICIPANTS: The Prostate cancer Research International: Active Surveillance (PRIAS) study is a multicenter prospective study of patients on AS (www.prias-project.org). We selected all patients undergoing MRI-Bx (targeted ± systematic biopsy) during AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A time-dependent Cox regression analysis was used to determine the predictors of GG progression/reclassification in patients undergoing MRI-Bx. A sensitivity analysis and a multivariable logistic regression analysis were also performed. RESULTS AND LIMITATIONS: A total of 1185 patients underwent 1488 MRI-Bx sessions. The time-dependent Cox regression analysis showed that age (per 10 yr, hazard ratio [HR] 0.84 [95% confidence interval {CI} 0.71-0.99]), MRI outcome (Prostate Imaging Reporting and Data System [PIRADS] 3 vs negative HR 2.46 [95% CI 1.56-3.88], PIRADS 4 vs negative HR 3.39 [95% CI 2.28-5.05], and PIRADS 5 vs negative HR 4.95 [95% CI 3.25-7.56]), prostate-specific antigen (PSA) density (per 0.1 ng/ml cm3, HR 1.20 [95% CI 1.12-1.30]), and percentage positive cores on the last systematic biopsy (per 10%, HR 1.16 [95% CI 1.10-1.23]) were significant predictors of GG reclassification. Of the patients with negative MRI and a PSA density of <0.15 ng/ml cm3 (n = 315), 3% were reclassified to GG ≥2 and 0.6% to GG ≥3. At the confirmatory biopsy, reclassification to GG ≥2 and ≥3 was observed in 23% and 7% of the patients diagnosed without upfront MRI and in 19% and 6% of the patients diagnosed with upfront MRI, respectively. The multivariable analysis showed no significant difference in upgrading at the confirmatory biopsy between patients diagnosed with or without upfront MRI. CONCLUSIONS: Age, MRI outcome, PSA density, and percentage positive cores are significant predictors of reclassification at an MRI-informed biopsy. Patients with negative MRI and a PSA density of <0.15 ng/ml cm3 can safely omit a protocol-based prostate biopsy, whereas in other patients, a multivariable approach is advised. Being diagnosed with upfront MRI appears not to significantly affect reclassification risk; hence, a confirmatory MRI-Bx cannot totally be omitted yet. PATIENT SUMMARY: A protocol-based prostate biopsy while on active surveillance can be omitted in patients with negative magnetic resonance imaging (MRI) and prostate-specific antigen density <0.15 ng/ml cm3. A confirmatory biopsy cannot simply be omitted in all patients diagnosed with upfront MRI.Peer reviewe

Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.Peer reviewe