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The article addresses the issue of local collaborative relationships between groups of different development actors in municipalities, as well as their perception of barriers to development. The study covered Polish municipalities that represent different dimensions of development dualism. The analyses used the results of 629 questionnaires and applied statistical analysis (Mann–Whitney Utest and Spearman’s rank correlation). The results indicate that the assessment of the importance of different types of relationships and barriers to development varies within some dualisms. At the same time, certain characteristics specific to certain dimensions of these dualisms can be discerned. The relationship between the importance of cooperation and the types of barriers to development showed no statistical significance or very weak relationships.

The subject of the paper are the grave robes of the Polish King Zygmunt III Vasa, resting in the crypt in the Archcathedral Basilica of Saint Stanislaus and Saint Wenceslaus on the Wawel Hill in Kraków. The studies presented were possible thanks to an ‘in situ’ analysis of the clothes and a possibility of taking samples of textiles from which the clothing was sewn. The paper presents the results of a comprehensive textile analysis of fabrics, a description of the clothing that made up the funerary robes and analysis of the results obtained in the context of historical sources and works of art depicting the monarch.

This study aims to identify and analyse the specific regulations of the Bankruptcy Law to the extent that they relate to the death of an insolvent debtor. The authors attempt to determine the correct interpretation de lege lata, and where it is justified, draw conclusions de lege ferenda. Due to the fact that regulations must be interpreted together with the provisions of inheritance law and other regulations, their correct interpretation may be difficult. This study contains an analysis of three possible cases: when death occurred after the filing of a bankruptcy petition, during the course of bankruptcy proceedings, but also on the brink of bankruptcy before the petition was filed by an authorized person. In the event of death after filing for bankruptcy or after its declaration, the problem is essentially of a procedural nature and is generally resolved by identifying the persons participating in the proceedings (usually a trustee). On the other hand, in the event of the death of an insolvent entrepreneur before they file for bankruptcy, the Bankruptcy Law provides for a separate procedure. At the same time, it seems that due to the distinctness of this situation, the introduction of a different, specific definition of insolvency is justified, which the authors present in this study.

Pembrolizumab and nivolumab (anty-PD-1 antibody) are commonly used for the treatment of melanoma patients. However, their efficacy and safety have never been directly compared, leaving little guidance for clinicians to select the best therapy. The study included patients with inoperable or metastatic melanoma treated in first line with anti-PD-1 immunotherapy (nivolumab or pembrolizumab). In total 1037 patients were enrolled in the study, 455 (44%) patients were treated with pembrolizumab and 582 (56%) with nivolumab. The estimated median overall survival (OS) in the pembrolizumab and nivolumab groups was 17.4 and 20.0 months [P = 0.2323; hazard ratio (HR), 1.1; 95% confidence interval (CI), 0.94–1.28], respectively, whereas the median progression-free survival (PFS) was 5.6 and 7.5 months (P = 0.0941; HR, 1.13; 95% CI, 0.98–1.29), respectively. The estimated 2- and 3-year OS in the pembrolizumab and nivolumab groups were 42/34% and 47/37%, respectively, and the PFS was 25/21% and 29/23%, respectively. There were 391 (49%) immune-related adverse events (irAEs) of any grade during treatment, including 133 (42%) related to pembrolizumab treatment and 258 (53%) to nivolumab treatment. A total of 72 (9.6%) irAEs were in G3 or G4, including during pembrolizumab 29 (9%) and nivolumab 48 (11%). There were no differences in OS, PFS and overall response rates between nivolumab and pembrolizumab therapy in previously untreated patients with advanced/metastatic melanoma. There were no differences in the frequency of G1/G2 or G3/G4 irAEs. The choice of treatment should be based on the preferences of the patient and the clinician.

The aim of the study was to evaluate the genetic structure of the reconstituted native Carpathian goat breed based on information from microsatellite markers. The study analysed of 14 microsatellite markers recommended by the International Society for Animal Genetics (ISAG) for goats individual identification and parentage testing. Blood samples were taken from 249 Carpathian goats from 14 farms. All microsatellite markers deployed in this analysis showed sufficient polymorphism to assess genetic variation in Carpathian goats and the ISAG-recommended panel for goat individual identification and parentage testing is a highly useful one. The present study showed the status of the genetic structure of the reconstituted population of Carpathian goats. Carpathian goats maintained in Poland were characterized by relatively high genetic diversity (the average of alleles per locus was 9.143), high values of heterozygosity and a low level of inbreeding coefficient. The obtained parameters indicate the correctness of the breeding activities carried out within the framework of the programme for the protection of genetic resources and give guidelines for taking further steps related to the breeding of this valuable native breed.

Aging-related neurological deficits negatively impact mental health, productivity, and social interactions leading to a pronounced socioeconomic burden. Since declining brain dopamine signaling during aging is associated with the onset of neurological impairments, we produced a selective dopamine transporter (DAT) inhibitor to restore endogenous dopamine levels and improve cognitive function. We describe the synthesis and pharmacological profile of (S,S)-CE-158, a highly specific DAT inhibitor, which increases dopamine levels in brain regions associated with cognition. We find both a potentiation of neurotransmission and coincident restoration of dendritic spines in the dorsal hippocampus, indicative of reinstatement of dopamine-induced synaptic plasticity in aging rodents. Treatment with (S,S)-CE-158 significantly improved behavioral flexibility in scopolamine-compromised animals and increased the number of spontaneously active prefrontal cortical neurons, both in young and aging rodents. In addition, (S,S)-CE-158 restored learning and memory recall in aging rats comparable to their young performance in a hippocampus-dependent hole board test. In sum, we present a well-tolerated, highly selective DAT inhibitor that normalizes the age-related decline in cognitive function at a synaptic level through increased dopamine signaling.

Abstract Allele frequencies for the 15 STR loci in the AmpF/STR® Identifiler™ kit (Applied Biosystems): D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, and FGA [...]

The purpose of this study was to synthesize a fluorine-18 labeled, highly selective aldosterone synthase (hCYP11B2) inhibitor, [18F]AldoView, and to assess its potential for the detection of aldosterone-producing adenomas (APAs) with positron emission tomography in patients with primary hyperaldosteronism (PHA). Using dibenzothiophene sulfonium salt chemistry, [18F]AldoView was obtained in high radiochemical yield in one step from [18F]fluoride. In mice, the tracer showed a favorable pharmacokinetic profile, including rapid distribution and clearance. Imaging in the adrenal tissue from patients with PHA revealed diffuse binding patterns in the adrenal cortex, avid binding in some adenomas, and “hot spots” consistent with aldosterone-producing cell clusters. The binding pattern was in good visual agreement with the antibody staining of hCYP11B2 and distinguished areas with normal and excessive hCYP11B2 expression. Taken together, [18F]AldoView is a promising tracer for the detection of APAs in patients with PHA.

Relations between metropolitan core cities and regional and sub-regional centres are part of a broader discussion on the importance of metropolitan areas for the development of regions. These relations are dealt with in this paper in the context of the growth pole theory. The paper focuses on the migration process in relation to enterprises. By moving their businesses, companies contribute to backwash and spread effects. Since company migrations between municipalities occur in both directions, the question remains open as to which migration direction dominates – whether from sub-regional centres to core cities or vice versa. This paper attempts to verify the hypothesis that regional and sub-regional centres in the Mazowieckie voivodship suffer the largest loss of enterprises due to migration to the core city of Warsaw. The results obtained were varied and the hypothesis was confirmed, especially in the case of three cities: Siedlce, Radom and Płock; and partly in the case of Ciechanów.

Supplemental Digital Content is available in the text.Despite considerable progress made in the treatment of patients with advanced melanoma, the majority of the patients treated with BRAF and mitogen-activated protein inhibitors (BRAFi and MEKi) experience a disease progression due to acquired resistance. Currently, ongoing studies explore the possibility to overcome or reverse this process. Our multicenter retrospective analysis included 51 patients with metastatic BRAF-mutated melanoma who had previously progressed on BRAFi/MEKi than had progressed on immunotherapy (anti-progression disease-1 or anti-cytotoxic T-lymphocyte-associated protein 4) and next were rechallenged with BRAFi/MEKi. Median age at BRAFi/MEKi rechallenge was 56 (range: 31–82 y/o). Median overall survival from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 29.7 and 9.3 months, respectively, whereas median progression-free survival was 10.5 and 5.9 months, respectively. Six-month, annual, and 2-year overall survival rates on both treatments were: 98% and 55%, 92% and 29%, and 69% and 2%, respectively. A response rate to treatment was higher in the group receiving BRAFi/MEKi for the first time as compared with the group receiving BRAFi/MEKi rechallenge and was overall response rate 72% and 27%; disease control rate 92% and 63%. Time interval between the end of the first BRAFi/MEKi treatment and the beginning of BRAFi/MEKi rechallenge did not influence median overall survival or progression-free survival. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. BRAFi/MEKi rechallenge treatment remains clinically important and is associated with the lower toxicity. BRAFi/MEKi rechallenge efficacy is higher in patients who are in good performance status, with normal lactate dehydrogenase, and without brain metastases.

The aim of the study was to evaluate the drug resistance of Enterococcus faecalisand Enterococcus faeciumisolated from different types of poultry waste. The study material consisted of feather samples (duck, turkey, chicken), sludge and centrifuge sediment, originating from three poultry farms. The study was conducted in two stages; isolation and identification of Enterococcusbacteria from the waste and evaluation of their drug resistance using Kirby-Bauer method. Contamination of the poultry waste with Enterococcusisolates included E. faeciumspecies (79 %) and E. faecalis(21 %). The most contaminated were sludge and sediment from the centrifuge as well as chicken feathers, irrespective of the place and time of sampling. Tested isolates showed multiple resistance and similar reaction to all antibiotics used in the study and E. faecalisstrain was more resistant. Enterococcusisolates showed the highest resistance to streptogramins, carbapenems, fluoroquinones, aminoglycosides and penicillins, and the lowest for nitrofurantions and phenicols.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor–immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.

The aim of the research was to assess the quality of milk from mountain sheep used for the production of traditional cheeses, taking into account the influence of the breed, the month of milking, and the content of somatic cells. Milk for the study was obtained from sheep of three mountain breeds: Podhale Zackel (PZ), Polish Mountain Sheep (PMS), and Coloured Mountain Sheep (CMS). The sheep were grazed in mountain pastures after lamb weaning, in the period from May to October in the traditional system. No influence of the breed on the examined parameters was found, except for urea content. Mountain sheep milk was characterized by a content of 19.68% solids, 8.48% fat, 6.63% protein, in which almost 76% was formed by casein (4.99%), and the average lactose content was 4.15%. Other milk parameters also did not differ between breeds: density was 1034.04 g/L, acidity 11.34°SH, and mean somatic cell content was 982.13∙103∙ml−1(log10SCC = 5.68). The highest urea content was recorded in the milk of Coloured Mountain Sheep (280.69 mg/L) and the lowest urea content was recorded in the milk of Zackel sheep (200.97 mg/L). The month of milking influenced the content of most milk components, but no changes in SCC content during lactation were found. Significant correlations between fat content and other milk parameters were recorded. In the case of urea content, negative, statistically significant correlations with the majority of examined parameters were found.

Given increased risk of cardiovascular events in asthma we hypothesized that lipoprotein-associated phospholipase A2(Lp-PLA2), an enzyme involved in atherosclerosis, is associated with proinflammatory and prothrombotic blood alterations in this disease.

Residual banana bulbs (RBB) were characterized and assessed as a potential starch and cellulose-based feedstock for bioethanol production. To facilitate the enzymatic digestibility, hydrothermal pretreatment was performed on RBB prior to simultaneous saccharification and fermentation (SSF) with Saccharomyces cerevisiae. Composition of RBB was similar to traditional starch and cellulose-based feedstocks with high glucan (60 g/100 gDM) and relatively low lignin content (7 g/100 gDM). Both amylase and cellulase were needed to efficiently hydrolyze RBB. The highest ethanol yield (310 kg EtOH/ton_DM_RBB, 93% of theoretical production based on total available glucose) was obtained with non-pretreated RBB. SSF can be carried out at lower RBB concentrations. Hydrothermal pretreatment affected negatively the bioethanol potential due to the loss of fermentable carbohydrates. In a case study of an African leading producer of bananas and plantains (Cameroon), the energy derived from bioethanol was 80 GWh ethanol/year and corresponded to 1.6% of the annual transportation requirement. This study shows that RBB is a promising alternative feedstock for bioethanol production.

AbstractThis essay, the last in a series, focuses on the relationship between Nietzsche’s mental illness and his philosophical art. It is predicated upon my original diagnosis of his mental condition as bipolar affective disorder, which began in early adulthood and continued throughout his creative life. The kaleidoscopic mood shifts allowed him to see things from different perspectives and may have imbued his writings with passion rarely encountered in philosophical texts. At times hovering on the verge of psychosis, Nietzsche was able to gain access to unconscious images and the music of language, usually inhibited by the conscious mind. He reached many of his linguistic, psychological and philosophical insights by willing suspension of the rational. None of these, however, could have been communicated had he not tamed the subterranean psychic forces with his impressive discipline and hard work.

Therefore the carried out study aimed at determination of the effect of high-calcium brown coal ash and compost being produced from municipal sewage sludge on the content and bioaccumulation of heavy metals in potato tubers, wheat grains and rapeseeds during a three-year period. Rapeseeds contained most Cd whereas wheat rains less. Potato tubers, wheat grains and rapeseeds contained more Mn, Ni and Zn in the fertilization objects with municipal sewage sludge with or without coal ash and compared to those where calcium carbonate or coal ash had been introduced into the soil at a dose corresponding to 1.5 Mg CaO · ha–1at the beginning of this study. Differences in the Mn, Ni and Zn contents in test plants between the fertilization objects with sewage sludge of with and without addition of ash were not significant.

This study used laboratory experiments to compare the effects of coal tar creosote on the activity of oxidoreductive enzymes in sandy loam, loamy sand and sandy clay loam soils. Different amounts of coal tar creosote were added to soil samples as follows: 0 (control), 2, 10 or 50 g kg-1 dry matter. The activity of soil dehydrogenases (DHAs), o-diphenol oxidase (o-DPO), catalase (CAT), nitrate reductase (NR) and peroxidases (POX) was determined. Contamination of soil with coal tar creosote affected oxidoreductase activity. Oxidoreductive enzyme activity following soil contamination with coal tar creosote was in the following order: DHAs > CAT > NR > POX > o-DPO in loamy sand and in sandy loam; and DHAs > POX > CAT > NR > o-DPO in sandy clay loam. The index of soil oxidoreductive activity (IOx) introduced in this study confirms the negative effect of coal tar creosote on oxidoreductase activity in soil. DHAs were the most sensitive to the contamination of soil with coal tar creosote. Moreover, the greatest changes in oxidoreductase activities were observed in loamy sand. Knowledge of the mechanism underlying the effects of coal tar creosote on oxidoreductive processes may enable development of a method for the bioremediation of polycyclic aromatic hydrocarbon-contaminated soils.

Neutrophil-to-lymphocyte ratio (NLR) has been shown to be prognostic in several solid malignancies. There are limited data regarding its value during novel therapies in patients with melanoma. The aim of the study was to assess the practical utility of this ratio in patients with BRAF-mutant melanoma treated with a combination of BRAF and MEK inhibitors (BRAFi/MEKi). We included 215 patients with inoperable or metastatic melanoma who underwent BRAFi/MEKi treatment between October 2015 and June 2017. Baseline NLR and other complete blood count-derived inflammatory markers were tested for association with overall survival and progression-free survival in univariate and multivariate models. On-treatment NLR was also assessed for relationship with these outcomes using the time-dependent Cox’s proportional hazard model. Prognostic model based on NLR and lactate dehydrogenase (LDH) levels was also developed. Patients with NLR values more than four had poorer progression-free survival (P<0.001, 1-year rates 51.6 vs. 26.7%) and overall survival (P<0.001, 1-year rates 77.3 vs. 53.1%). In a multivariate model adjusted for LDH levels, metastatic sites and age baseline NLR ratio and delay in starting MEKi were deemed statistically significant (hazard ratio: 1.81; 95% confidence interval: 1.16–2.85; P=0.009 and hazard ratio: 2.06; 95% confidence interval: 1.24–3.44, P=0.005 respectively). In a model based on NLR and LDH, 1-year survival rates were 57, 40 and 23%, respectively if zero, one or both factors were elevated. Our results demonstrate the usefulness of NLR and a predictive model based on combinations of NLR and LDH as a prognostic markers during BRAFi/MEKi treatment. Our real-world data confirm the efficacy of BRAFi/MEKi therapy showed in the clinical trials.

Herein, we report a novel intramolecular ring-closing reaction of biaryl thioethers that give access to highly functionalized dibenzothiophene sulfonium salts under mild conditions. The resulting precursors react regioselectively with [18F]fluoride to give [18F]fluoroarenes in predictable radiochemical yields. The strategy expands the available radiochemical space and provides superior labeling efficiency for clinically relevant PET tracers.

One of the methods for recovery and utilization of waste products from the poultry industry is to subject them to the methane fermentation process in the biogas plant. These are waste with a high content of fatty compounds and proteins, including keratin. Their specificity is characterized by rapid possibility of spoilage, rancidity and problems of further management. These wastes are characterized by varying degrees of complexity, thus their use as a raw material for the biogas fermenter should be preceded by a pre-treatment. An example of waste generated in poultry processing is biological sludge. Optimizing this material with highly enzymatic fungi could accelerate the degradation of the organic matter contained and, as a result, increase the energy efficiency of this type of waste. Quantitative and qualitative parameters of biogas produced from biological sludge processed by isolated filamentous fungi with high metabolic potential were determined. Laboratory tests were based on the modified methodology included in the standards DIN 38414-S8 and VDI 4630. Based on the results obtained, it was found that the pre-optimization of biological sludge by fungal strains with different metabolic potential, influences on the yield of biogas production, including methane. There was an increase in the biogas yield from the biological sludge processed by the mixed fungal consortium (by 20 %) and the strain marked as F1 (by 14 %) as compared to the non-inoculated material, which was also reflected in the amount of methane produced in the case of the mixed fungal consortium (by 28 %) and the strain marked as F1 (by 12 %).

Toxoplasma gondiiand Neospora caninumare coccidian parasites with a global distribution that cause reproductive failure and production losses in livestock. The seroprevalence of both parasite species in ruminants and Cervidaehas been investigated worldwide and found to vary greatly. Studies carried out on mixed flocks with 3 ruminant species (sheep, goats, and fallow deer) living under the same conditions are excellent models for identifying any differences in the rate of infection with the 2 parasites between the animal species. Additionally, the species used in the present study differ in their feeding categories: grazers, browsers, and intermediate feeders. The aim of the study is to identify any variation in the prevalence of the 2 parasites in mixed flocks and to identify any possible relationships with food choice. The seroprevalence against T. gondiiand N. caninumin 167 captive fallow deer, 64 sheep, and 39 goats were detected using commercially available ELISA. The seroprevalence for T. gondiiachieved 10% in fallow deer, 21% in goats, and 47% in sheep. The seroprevalence for N. caninumachieved 13% in sheep and fallow deer and 21% in goats. Overall, 53% of the sheep, 33% of the goats, and 22% of the fallow deer were seropositive for both infections. Coinfection of T. gondiiand N. caninumwas detected in 6% of sheep, 8% of goats, and 2% of fallow deer. Statistical analyses of the seroprevalence levels observed between 2 parasites for each animal species revealed that only the results obtained for sheep were significant (P< 0.01). Additionally, the differences in the seroprevalence levels for T. gondiibetween sheep and goats and between sheep and fallow deer were statistically significant (P< 0.01). The results of the N. caninumseroprevalence levels observed among animal species were not significant. Although the variations in susceptibility to T. gondiiand N. caninuminfections demonstrated by the examined animals may affect the differences in seropositivity, these appear to be related to the feeding habits of the animal species. Therefore, the risk of infection by agents found close to the ground, such as coccidian oocysts, varies. Sheep as grazers are at a greater risk of infection by T. gondiithan goats and fallow deer.

High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and mortality from gynecologic malignant tumors. Overall survival remains low because of the nearly ubiquitous emergence of platinum resistance and the paucity of effective next-line treatments. Current cell culture–based models show limited similarity to HGSC and are therefore unreliable predictive models for preclinical evaluation of investigational drugs. This deficiency could help explain the low overall rate of successful drug development and the decades of largely unchanged approaches to HGSC treatment. We used gene expression, copy number variation, and exome sequencing analyses to credential HGSC patient–derived xenografts (PDXs) as effective preclinical models that recapitulate the features of human HGSC. Mice bearing PDXs were also treated with standard-of-care carboplatin therapy. PDXs showed similar sensitivity to carboplatin as the patient's tumor at the time of sampling. PDXs also recapitulated the diversity of genomic alterations (copy number variation and mutation profiles) previously described in large data sets that profiled HGSC. Furthermore, mRNA profiling showed that the PDXs represent all HGSC subtypes with the exception of the immunoreactive group. Credentialing of PDX models of HGSC should aid progress in HGSC research by providing improved preclinical models of HGSC that can be used to test novel targets and more accurately evaluate their likelihood of success.

Microorganisms, usually invisible for us, accompany us always and everywhere. Often we do not realize how decisive its impact on our lives is, how much we use their presence, which of our troubles are the result of their actions, and also how surprising effects result from their activity. Microorganisms also very often play a decisive role in the development of societies, politics and history. One of the most spectacular interventions of micro-organisms in human history include the example of a false “oil fever” that exploded in Australia in the second half of the nineteenth century. It was even more significant to redirect Europe's history in the new direction as a result of the “black death” epidemic in the fourteenth century. Microorganisms have created social conditions for the transition to the next epoch - renaissance, which forms the basis of today's shape. Because of the microorganisms J.F. Kennedy could have been in the 1960 President of the United States of America and to direct her development in the new direction and to stop Khrushchev's expansion into the second hemisphere. Microorganisms, not leaders and generals, won battles and wars. It was Rikketsia prowazeki, not the genius of the opponents, that broke Napoleon's power in Europe. Microorganisms fight disease, improving quality of life and prolonging its period. They allowed to control rabies and numerous infectious diseases. In the economy for the cause of microorganisms, powerful monopolies fell. Bacteria were also used to protect civilians in Poland during World War II. There are many similar stories to tell, stories in which microorganisms play an essential role. But would these stories be about microorganisms only? Or perhaps about people who were fascinated by the microscopic world of microbes discovered his secrets, meaning and ... beauty.

AbstractNietzsche’s name has become almost synonymous with militant atheism. Born into a pious Christian family, this son of a Lutheran pastor declared himself the Antichrist. But could this have been yet another of his masks of hardness? Nietzsche rarely revealed his innermost self in the published writings, and this can be gleaned mainly from his private letters and the accounts of friends. These sources bring to light the philosopher’s inner struggle with his own, deeply religious nature.Losing his father at a young age was a calamity from which Nietzsche never recovered, and I argue that his famous thought-image “God is dead” was a transfiguration of the painful memory of this loss. In this essay, I trace Nietzsche’s tortuous path from an ardent devotee of God to a vociferous critic of Christianity, a path that was punctuated with veiled longings for a loving deity. Deep in his heart, he remained faithful to Christian ideals. Rather like Cordelia, the only truly loving daughter of King Lear, Nietzsche refused to utter words of intense affection and reverence, as these had been blatantly devalued and corrupted. Instead, he adopted a mask of a wrongdoer and a blasphemer who took not the punishment but the guilt.Nietzsche’s attitude to religion is discussed from the perspective of his life, his personality, and his mental condition. The discussion draws on psychoanalytical concepts of Freud, Erikson, Winnicott and Kohut. This is not an exclusive reading, but complementary to other studies in this field.

The conservation of farm animal genetic resources and their protection against genetic erosion requires knowledge of biodiversity status. Genetic variation in populations can be estimated using both traditional pedigree-based methods and molecular techniques. SNP microarrays are a new generation of molecular genetic tools, which have found application in analysis of biodiversity in populations of domestic and wild sheep, in studies of resistance to intestinal parasites and foot rot, and in searching for markers associated with meat and milk yield, or colour inheritance traits. The aim of the study is the review of recent literature on the biodiversity and the use of molecular markers for population genetics in different breeds and populations of sheep.

Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma.

AbstractThis paper addresses the questions raised by the evidence presented that many cardinal psycho-analytic notions bear a strong resemblance to the ideas of Schopenhauer and Nietzsche. In the process, the author considers not only that the 19th century Zeitgeist, given its preoccupation with the unconscious, created a fertile ground for the birth of psychoanalysis, but the influence on the Weltanschauung of Freud, Schopenhauer and Nietzsche of their common German cultural heritage, their shared admiration for Shakespeare and love of Hellenic culture, and the meteoric rise of science. Although influence may not be sharply separated from confluence, the parallels between Freud's concepts and those of Schopenhauer and Nietzsche are too specific to be coincidental. And yet, Freud vehemently denied ever having read these philosophers’ works until “very late in life”. It is suggested that an unconscious sense of guilt may have induced that denial.This study adopts a cross-sectional approach that juxtaposes Freud's cardinal concepts with the ideas of Schopenhauer and Nietzsche. Its tripartite structure has the advantage of observing similarities and differences not only between Freud and the two philosophers, but also between Nietzsche and Schopenhauer. The focal concepts include: the unconscious; ego, id and superego; libido; drives; repression; sublimation; dreams; catharsis; free association; primary and secondary process thinking; Oedipus complex; repetition compulsion; the pleasure principle; mourning and melancholia; a criminal from a sense of guilt; and the death instinct.

AbstractNietzsche's notion of the Übermensch is one of his most famous. While he himself never defined or explained what he meant by it, many philosophical interpretations have been offered in secondary literature. None of these, however, has examined the significance of the notion for Nietzsche the man, and this essay therefore attempts to address this gap.The idea of the Übermensch occurred to Nietzsche rather suddenly in the winter of 1882-1883, when his life was in turmoil after yet another deep personal setback. The early loss of his father had deprived Nietzsche of a meaningful “mirroring” and a chance to experience realistic, age appropriate disappointment. This left him with a lifelong tendency towards idealisation. It became his proverbial Achilles’ heel and the source of repeated disillusionments and sorrow. The Übermensch may thus have been a culmination of his impulse to create altars and worlds before which he could kneel. Trying to cope with his own vulnerability, Nietzsche evoked an ideal of the Übermensch, a mask of hardness that was designed, if unconsciously, to ward off any future assaults on his fragile self.The double aspect of Nietzsche's personality is explored in this essay. While a highly provocative, belligerent and uncompromising Nietzsche often emerges from his published works, a vulnerable, lonely and sometimes self-pitying Nietzsche lurks in his letters and the accounts of his friends and acquaintances. But could an “ideal of strength”, such as the Übermensch, serve as a protective mask for someone with a sensitive, passionate interior? Nietzsche's descent into madness would suggest that no ideal can be a substitute for human, all too human, compassion.

Proteasome machinery is a major proteostasis control system in human cells, actively compensated upon its inhibition. To understand this compensation, we compared global protein landscapes upon the proteasome inhibition with carfilzomib, in normal fibroblasts, cells of multiple myeloma, and cancers of lung, colon, and pancreas. Molecular chaperones, autophagy, and endocytosis-related proteins are the most prominent vulnerabilities in combination with carfilzomib, while targeting of the HSP70 family chaperones HSPA1A/B most specifically sensitizes cancer cells to the proteasome inhibition. This suggests a central role of HSP70 in the suppression of the proteasome downregulation, allowing to identify pathways impinging on HSP70 upon the proteasome inhibition. HSPA1A/B indeed controls proteasome-inhibition-induced autophagy, unfolded protein response, and endocytic flux, and directly chaperones the proteasome machinery. However, it does not control the NRF1/2-driven proteasome subunit transcriptional bounce-back. Consequently, targeting of NRF1 proves effective in decreasing the viability of cancer cells with the inhibited proteasome and HSP70.

Basing on long-standing cyclic measurements of sludge-originated biogas composition and considering statistical analysis of their results, a regression model describing time variation of biogas desulfurization using bog iron ore has been developed. The model was verified by theoretical calculations and results from laboratory examinations of the sorbent. It was also used to estimate the depletion time and sorption capacity of the bed and to determine the demand index for bog ore.

Familial hypercholesterolemia (FH) is a genetic disease that causes accelerated atherosclerosis and a high risk of occurrence of cardiovascular events. Atherosclerosis in the course of FH develops insidiously and reaches an advanced stage before the onset of clinical symptoms. Homozygous form of FH occurs in the Caucasian population with a frequency of one per million, while the heterozygous form of FH in European countries applies on average in 1 person per 500. FH diagnosis is an indication to take the whole family under medical care, education, and to introduce dietary and pharmacological treatment. The aim of treatment in children with FH is to achieve more than 50% reduction in LDL level or to achieve LDL-cholesterol concentrations below 130mg/dl and below 100mg/dl in diabetic children. The effectiveness of low fat diet in the treatment of FH is limited. The medicaments of first choice in the treatment of FH are statins. After initiation of therapy in children, cholesterol levels and the side effects of therapy and its impact on children's development, nutritional status, degree of sexual maturity should be routinely evaluated. Familial hypercholesterolemia is a relatively common metabolic disorder, but still quite rarely recognized and not properly treated. Early diagnosis and appropriate treatment of FH in children and adolescents can significantly reduce the risk of cardiovascular disease and sudden death in adults. The purpose of these recommendations is to describe the current epidemiological situation in Poland, to establish the guidelines for identifying FH in children and adolescents and to enable the introduction of effective treatment.

AbstractThis essay is an interpretation of Nietzsche’s enigmatic idea of the Eternal Return of the Same in the context of his life rather than of his philosophy. Nietzsche never explained his ‘abysmal thought’ and referred to it directly only in a few passages of his published writings, but numerous interpretations have been made in secondary literature. None of these, however, has examined the significance of this thought for Nietzsche, the man. The idea belongs to a moment of ecstasy which Nietzsche experienced during the summer of 1881 in Sils-Maria, in the Swiss Alps. Like Dante, in ‘the middle of life’, he walked down the wooded Alpine slope and entered his own Inferno. On the anniversary of long-buried loss and pain, his psyche was temporarily flooded by archetypal imagery. This event is interpreted in the light of Freud’s theory of repetition compulsion, the uncanny, and the oedipal confrontation with the unconscious. From the turbulent and frightful experience, a symbol of transfiguration emerged in the shape of Eternal Return. Its likeness to Mandala, a Jungian archetype of wholeness and the self, is striking. In the years that followed, Nietzsche produced his greatest works that assured him an unassailable place in Western philosophy. And yet, there was something disturbing about this dream-thought, and Nietzsche shuddered at any mention of the thought. Linking it with the head of Medusa in his unpublished notes, he hinted at its petrifying quality. The beguiling beauty of Medusa makes her an ambiguous symbol of exhilaration, as well as terror. Under her captivating gaze, a hero’s journey towards selfhood becomes a journey into the night of madness.

Immediate needs after sexual assault include safety and privacy in the first instance, followed by treatment of injuries and prevention of unwanted pregnancy and sexually transmitted infections, including human immunodeficiency virus. Management should include risk identification of self-harm and suicide, as well as safeguarding children and vulnerable adults. Pregnancy prevention can be achieved through oral or mechanical methods of emergency contraception. Availability of emergency contraception may vary between districts and countries, depending on local laws and cultural or religious beliefs. Sexually transmitted infections, including gonorrhoea, chlamydia, hepatitis B and human immunodeficiency virus, represent an important part of management of victims of sexual assault. They can be prevented immediately by offering bacterial and viral prophylaxis followed by sexual health screening 2 weeks later unless symptomatic. In deciding what antibiotics to use as prophylaxis, local prevalence of infections and resistance to antibiotics should be considered. Prophylaxis against human immunodeficiency virus infection after sexual exposure should be discussed and offered in high-risk cases for up to 72h after exposure. This should be accompanied by baseline human immunodeficiency virus test and referral for follow up. In high prevalence areas, prophylaxis against human immunodeficiency virus infection after sexual exposure should be offered as a routine. Psychosocial support and risk assessment of vulnerabilities, including self-harm or domestic violence and practical support should be addressed and acted on depending on identified needs.

While rape and sexual assault are common, most offences remain unreported. These crimes are associated with acute and chronic physical and psychological morbidity and may be linked to substance misuse, healthcare neglect, ‘risky’ sexual behaviour and eating disorders. Early interventions may reduce serious psychological morbidity in some individuals. Most research focuses on the impact of sexual violence on women, but the principles of management apply to both male and female complainants.

AbstractNietzsche’s cardinal ideas - God is Dead, Übermensch and Eternal Return of the Same – are approached here from the perspective of psychiatric phenomenology rather than that of philosophy. A revised diagnosis of the philosopher’s mental illness as manic-depressive psychosis forms the premise for discussion. Nietzsche conceived the above thoughts in close proximity to his first manic psychotic episode, in the summer of 1881, while staying in Sils-Maria (Swiss Alps). It was the anniversary of his father’s death, and also of the break-up of his friendship with Wagner, the most important relationship in his life. Despite having been acquainted with these ideas from reading philosophy and literature, Nietzsche created them de novo and imbued them with very personal meaning. Surprisingly, he never defined or explained his cardinal thoughts in his published writings, perhaps because rationally he could not. A resultant hermeneutic vacuum provoked an avalanche of interpretations in secondary literature. But could these ideas be delusions? A current definition of delusion is challenged, and an attempt is made at a limited comparison between delusion, scientific/philosophical doctrine and poetic creation. It is also argued that psychosis is a way of re-living trauma, and delusions can therefore be seen as a form of reasoning that helps to make sense of the world in a state of psychotic disintegration. Far from being false beliefs, delusions are a true expression of one’s innermost feelings and pain, albeit indirectly. The relationship between early parental loss and repeated trauma, psychosis and creativity is also explored.

In order to find the origin of crystalline defects occurring in the preparation of InAs/GaAs quantum dots (QDs), their appearance was tracked through three different sample types designed as Schottky diodes. Specimens with a GaAs cap layer on a GaAs buffer layer as well as with an InAs wetting layer without QDs were grown by molecular beam epitaxy (MBE) using the interrupted growth technique. Deep level transient spectroscopy (DLTS) was used for comparison with structures containing InAs QDs. It was found that two main levels with thermal activation energies of 0.14–0.16 eV and 0.46–0.52 eV from the conduction band edge, respectively, are grown-in defects, which are characteristic of the growth interrupted interface occuring under an excess of As. Both these levels together with an additional level at 0.10–0.12 eV found in the InAs wetting layer structures were also present in those with QDs, probably resulting from strain or In penetration. All three defects were agglomerated close to the interface created by the interrupted growth. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

R-CHOP immunochemotherapy remains standard frontline therapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients. However, this therapy is ineffective in approximately 1/3 of patients, underscoring the need for better treatment modalities. Targeting DLBCL oncogenic drivers is a promising strategy to improve the treatment efficacy and outcome. Although MYC transcription factor is one of the key oncogenes in DLBCL development, direct MYC targeting strategies have been largely ineffective, highlighting the need for other, indirect approaches. For example, MYC expression is stabilized by PIM serine-threonine kinases, indicating that PIM inhibition might be a rational approach to indirectly target MYC. In this study, we assessed the PIM-MYC relationship and the consequences of PIM inhibition in DLBCL. We first evaluated the expression of PIM1-3 and MYC proteins in 57 DLBCL diagnostic sections by immunohistochemistry. In this series, 70.17% of specimens were positive for at least one PIM isoform and 84.22% cases were MYC-positive. 100% of cases with high MYC expression (MYC present in ≥30% of the cells, n=35) were PIM-positive, whereas 86,36% of cases with undetectable or low MYC expression (MYC detected in ≤20% of cells, n= 22) were PIM-negative (Fisher’s exact test, p<0.0001). Since the coexpression of MYC and PIMs highlights the functional link between these proteins in DLBCLs, we evaluated the expression of PIM kinases in cell lines following siRNA-mediated MYC knockdown or treatment with MYC-MAX dimerization inhibitor, 10058F4. The genetic or chemical MYC inhibition markedly decreased PIM1-3 expression in six GCB and ABC cell lines. Likewise, knockdown of all three PIM isoforms decreased MYC levels, attenuated proliferation and induced apoptosis. Similarly, PIM blockade with SEL24/MEN1703, a novel pan-PIM/FLT3 inhibitor tested currently in clinical trial in AML patients and exhibiting favorable safety profile, decreased the expression of multiple MYC-dependent genes. To assess the MYC role in PIM inhibitor-mediated toxicity, we generated DHL4 cells expressing degradation-resistant MYC_T58A mutant. MYC_T58A expression partially protected cells from PIM inhibitor-induced proliferation arrest and apoptosis, indicating that the inhibitor’s toxicity is at least partially mediated by MYC depletion.

Abstract: The enthalpies of solution of Co(II) and Na(I) trifluoromethanesulfonates (triflates) in N,N-dimethylformamide (DMF)–methanol (MeOH) mixtures have been measured over the whole range of solvent composition. From these data the enthalpies of transfer of Co(II) and triflate ions from methanol to the mixed solvent have been determined usingliterature values of the enthalpies of transfer of the Na+ ion. The results have been analyzed by means of the theory of preferential solvation. The analysis revealed the preference of DMF for solvating the Co(II) ion in the MeOH-rich region of solvent composition and the lack of preference of any component in the DMF-rich region. Visible absorption spectra of the Co(II) ion in DMF–MeOH mixtures have been also measured in the whole range of solvent composition and analyzed using the partial least-squares method. The mean composition of the solvation sphere of the Co(II) ion versus solvent composition has been determined on the basis of both analyses. The results were found to be consistent with each other and with those obtained previously from FT-IR spectra.

Obsessive-compulsive disorder, classified as an anxiety disorder, arises from malfunctioning of the fronto-striatalpallido-thalamic-frontal circuit in the brain. As well as perseverative thoughts and acts, there are other signs of ‘organicity’. Delay in treatment is often a result of patients' reluctance to seek help, and doctors' insufficient knowledge and experience in this clinical area. Electroconvulsive therapy is effective in severe and refractory cases.

The odd–odd 58Co nucleus has been studied with the 51V(10B, p2n) reaction at 33 MeV and 36 MeV incident energy using the γ-spectrometer Saci-Pererê. Excited states up to 8.0 MeV and spin up to 11+ have been observed. DSAM lifetimes for 13 excited states were measured. The results are compared to shell model calculations using the GXPF1 effective interaction, developed for use in the fp shell.