Business recovery and institutional constraints: evidence from Visegrad Countries and Serbia

The current study investigates how institutional constraints and firms’ and entrepreneurs’ characteristics affect business recovery. Some elements have not yet been rigorously examined in the existing literature, especially not concerning the post-communist countries’ business recovery component and the same is the research gap current study intended to address. To evaluate the study model, ordinal logistic regression was used. More than 300 valid questionnaires are collected from the Czech Republic, Hungary, and Serbia. The findings show that factors such as firm tenure and size, location, sector, entrepreneurial motivation, product change, etc., have conflicting effects on business recovery. Some of the outcomes of the present study is supported by the existing studies and some requires further research. The study focuses on the less explored independent variables and their association with business recovery, specifically on SMEs, which highlights the paper’s originality. The output of the current study adds to the existing literature of business recovery and institutional constraints. Policymakers interested in removing institutional limitations and promoting a quicker business recovery for SMEs are drawn to the research. The study findings are also helpful from a managerial standpoint because business owners and managers significantly impact decisions about entrepreneur motivation, product change, and other issues

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience

IntroductionProstate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging.AimThe integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease.Patients and methodsThe data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration.ResultsFrom 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07–0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described.ConclusionPSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT

Safety & efficacy of lifileucel (LN-144) tumor infiltrating lymphocyte therapy in metastatic melanoma patients after progression on multiple therapies – independent review committee data update

Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel, a centrally manufactured cryopreserved autologous TIL therapy assessed by both investigator and an independent review committee (IRC), are presented

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Shifts Between Search Stages During Task-performance in Mediated Information Seeking Interaction

The research reported here focuses on the users' information seeking behavior. Set in the framework of the interactive information retrieval paradigm, the research examines the micro-dynamics of the information seeking process, and explores search stages that users pursue as they proceed to solve their information problem. The research analyzes the users' information seeking behavior as they move between search stages, and looks for patterns in the transition. The observed shifting behavior allows for examining the question of predictability. The observed shifting patterns lead to the development of a new model for information seeking behavior that describes multiple search stages, aspects and dimensions. The model represents a non-linear process of multiple re-iterative cycles that make up the overall flow of communication with the information system. The model expands significantly earlier theoretical and empirical models as it represents a series of re-iterative processes that characterize the information seeking interaction

Why do we need a more locally focused rural employment policy in the EU

In practice the EU suggestions are translated mechanically to national and regional policies, in many instances, without taking into account the real interests and needs of the inhabitants at different regional levels. This way the capitalization of EU policies and funds is not as efficient as it should be since the endogen potentials of localities are not utilized properly. Our hypothesis is that the rural areas of the EU are so diverse that the significant differences in employment, economic, social, educational and infrastructural features of rural regions necessitates a more locally focused policy which could be supported by analyse statistical data. The analysis is based on the Eurostat General and Regional database and on national statistical databases. What are the reasons that one size fits all solutions has to be avoided and has to be changed with locally adapted policies? Probably this question can be answered partly by the facts of statistical data with which the differences, in some cases extremely huge alterations amongst territorial features, can be demonstrated. Differences based on ruralty are a common topic of rural policies and rural science in EU countries however the differences in rural features of different countries may be notably important. Analysing the employment-unemployment indicators and those indicators that closely related to employment we found that in many instances the major differences are between the post-socialist new member states (NMS) and the EU 15 countries

NEW SOURCES OF EMPLOYMENT TO PROMOTE THE WEALTH-GENERATING CAPACITY OF RURAL COMMUNITIES

New Sources of Employment to Promote the Wealth-Generating Capacity of Rural Communities (acronym: RuralJobs) is a collaborative research project partly funded under the European Commission Research and Development 7th Framework Program. The RuralJobs consortium consists of partners drawn from eight European Union (EU) countries (Bulgaria, France, Hungary, Italy, Lithuania, Romania, Spain and UK). The project began on February 2008 and finished in October 2010. RuralJobs quantified labour market, demographic and economic trends, and the impact of employment creation measures and policies in seven, representative “reference areas” across the EU, and used the information to demonstrate how rural development measures can be better targeted and how rural development policies should evolve.We identified labour market, demographic and economic trends in rural areas across EU-27 and the potential for new sources of employment outside traditional primary and secondary sector activities, and examined the interaction between different types of rural area (peri-urban, remote, high environmental/amenity value etc.). We identified employment growth areas where rural development programmes can be targeted to increase their contribution to employment creation. Our strategic objectives were the following: review of employment policies and programmes, scenarios for new sources of employment according to rural typologies, recommendations for better targeting of strategies, dissemination and mainstreaming. The main outcome expected is that the results will allow a better targeting of rural development measures and future evolution of rural development policies in line with the Lisbon Strategy