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

Renal function remains after unilateral total and contralateral partial nephrectomy : an experimental study in pigs using 99mTc-DTPA

Peer reviewe

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

Combined Surgical Treatment for Chronic Upper Extremity Lymphedema Patients Simultaneous Lymph Node Transfer and Liposuction

Background Upper limb lymphedema is a common problem after axillary lymph node dissection. Lymphatic drainage can be improved by microvascular lymph node transfer, whereas liposuction can be used to reduce arm volume and excess of adipose tissue. We present the results of chronic lymphedema patients who have undergone lymph node transfer and liposuction simultaneously in 1 operation and compare the results with patients who have undergone lymph node transfer without liposuction. Methods During May 2007 to February 2015, 20 postmastectomy patients and 1 Hodgkin's lymphoma patient presenting with chronic nonpitting lymphedema (age between 37 and 74 years, average 56.7 years) were operated using the combined technique and 27 postmastectomy patients presenting with early-stage lymphedema (age between 31 and 68 years, average age 50.2 years) were operated using only the lymph node transfer. Compression therapy was started immediately after the operation and the patients used compression 24 h/d at least 6 months postoperatively. Changes in clinical parameters (number of erysipelas infections, pain), arm volume, transport indexes calculated form lymphoscintigraphy images, and daily usage of compression garments were compared preoperatively and postoperatively and between groups (combined technique vs lymph node transfer). The study was a retrospective observational study. Results In the combined technique group, the average arm volume excess decreased postoperatively 87.7%, and in 7 of 10 patients, the edema volume did not increase even without compression. Seventeen of 21 patients were able to reduce the use of compression garment. Lymphoscintigraphy results were improved in 12 of 15 patients and the improvement was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.01). The number of erysipelas infections was decreased in 7 of 10 patients and the decrease was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.02). In the lymph node transfer group, the average excess volume decreased postoperatively 27.5%. Fourteen of 27 patients were able to reduce the use of compression garments. Lymphoscintigraphy results were improved in 8 of 19 patients, and the number of erysipelas infections was decreased in 1 of 3 patients. Conclusions Liposuction can safely be performed with lymph node transfer in 1 operation to achieve optimal results in patients with chronic lymphedema. The combined technique provides immediate volume reduction and further regenerative effects on the lymphatic circulation. The significantly greater reduction in lymphoscintigraphy values and erysipelas infections suggests that the combined technique might be better for late-stage lymphedema patients than lymph node transfer alone

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

ITGB1-dependent upregulation of Caveolin-1 switches TGF beta signalling from tumour-suppressive to oncogenic in prostate cancer

Caveolin-1 (CAV1) is over-expressed in prostate cancer (PCa) and is associated with adverse prognosis, but the molecular mechanisms linking CAV1 expression to disease progression are poorly understood. Extensive gene expression correlation analysis, quantitative multiplex imaging of clinical samples, and analysis of the CAV1-dependent transcriptome, supported that CAV1 re-programmes TGF beta signalling from tumour suppressive to oncogenic (i.e. induction of SLUG, PAI-1 and suppression of CDH1, DSP, CDKN1A). Supporting such a role, CAV1 knockdown led to growth arrest and inhibition of cell invasion in prostate cancer cell lines. Rationalized RNAi screening and high-content microscopy in search for CAV1 upstream regulators revealed integrin beta1 (ITGB1) and integrin associated proteins as CAV1 regulators. Our work suggests TGF beta signalling and beta1 integrins as potential therapeutic targets in PCa over-expressing CAV1, and contributes to better understand the paradoxical dual role of TGF beta in tumour biology.Peer reviewe

Expert consensus document: Semantics in active surveillance for men with localized prostate cancer — results of a modified Delphi consensus procedure

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making

Long-term Results of Microvascular Lymph Node Transfer: Correlation of Preoperative Factors and Operation Outcome

Background: Our objective was to analyze whether a correlation could be observed between preoperative factors and microvascular lymph node transfer outcome after long-term follow-up.Methods: We included 67 patients in this retrospective case series. The incidence of cellulitis, the difference of arm circumference, the use of the compression garments both preoperatively and postoperatively, and subjective symptoms, such as pain, were analyzed. Volumetry and lymphoscintigraphy results were also analyzed in a subgroup of patients. We correlated preoperative factors with postoperative results.Results: After 70 +/- 17 months of follow-up, 42% of the patients were able to discontinue the use of compression garments. The subjective pain symptoms were reduced in 75% of the patients. The incidence of cellulitis was reduced from preoperative 0.20 +/- 0.55/y to postoperative 0.02 +/- 0.08/y. As a novel finding, the patients with preoperative cellulitis were more likely to continue the use of the compression garments.Conclusions: The surgery is beneficial to most studied lymphedema patients, although it is not the cure for all patients. The incidence of cellulitis was reduced, and further, the presence of preoperative cellulitis seems to affect the outcome of the operation.</p

Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors : Results from a Phase I/II Clinical Trial

Purpose: Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages toward a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition of the macrophage scavenger receptor Clever-1 has shown benefit in inducing CD8 T-cell-mediated antitumor responses in mouse models of cancer, which supports the clinical development of Clever-1-targeting antibodies for cancer treatment. Patients and Methods: In this study, we analyzed the mode of action of a humanized IgG4 anti-Clever-1 antibody, FP-1305 (bexmarilimab), both in vitro and in patients with heavily pretreated metastatic cancer (n = 30) participating in part 1 (dose-finding) of a phase I/II open-label trial (NCT03733990). We studied the Clever-1 interactome in primary human macrophages in antibody pull-down assays and utilized mass cytometry, RNA sequencing, and cytokine profiling to evaluate FP-1305-induced systemic immune activation in patients with cancer. Results: Our pull-down assays and functional studies indicated that FP-1305 impaired multiprotein vacuolar ATPase-mediated endosomal acidification and improved the ability of macrophages to activate CD8(+)T-cells. In patients with cancer, FP-1305 administration led to suppression of nuclear lipid signaling pathways and a proinflammatory phenotypic switch in blood monocytes. These effects were accompanied by a significant increase and activation of peripheral T-cells with indications of antitumor responses in some patients. Conclusions: Our results reveal a nonredundant role played by the receptor Clever-1 in suppressing adaptive immune cells in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch, potentially leading to intratumoral proinflammatory responses in patients with metastatic cancer.Peer reviewe