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To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide, we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase-1 (COX-1) and -2 (COX-2) and endothelial (NOS-3) and inducible (NOS-2) nitric oxide synthase in rat lungs. Anesthetized, tracheotomized, and ventilated rats received 3 mL/kg human meconium suspension intratracheally (n = 19), and 14 control rats received an equal volume of saline. Ten rats were pretreated with indomethacin, and 13 rats were pretreated with dexamethasone. The lungs were ventilated with 70% oxygen for 3 h after the insult, and the level of COX-1, COX-2, NOS-2, and NOS-3 mRNA in lung tissue was analyzed by Northern blot hybridization. Furthermore, the expression and localization of the enzyme proteins was analyzed by immunohistochemistry. COX-1 and NOS-3 were clearly expressed in the lungs of control rats, whereas the level of COX-2 and NOS-2 expression was minimal. Meconium administration did not affect the expression of COX-1, but COX-2 expression was up-regulated in the respiratory epithelium and alveolar macrophages. Meconium also induced up-regulation of NOS-2 in the pulmonary epithelium, vascular endothelium, and macrophages. Indomethacin pretreatment did not affect the enzyme expressions, whereas dexamethasone administration significantly inhibited the meconium-induced COX-2 and NOS-2 up-regulation. Our data thus indicate that intrapulmonary meconium up-regulates lung COX-2 and NOS-2 gene expression, suggesting an important role for prostaglandins and nitric oxide in the meconium aspiration-induced pulmonary inflammation and hemodynamic changes.

Several types of endocrine tumors show frequent somatic deletions of the distal part of chromosome arm 11q, where the tumor-suppressor gene SDHD (succinate-ubiquinone oxidoreductase subunit D), constitutionally mutated in paragangliomas of the head and neck, is located. In this study, we screened 18 midgut carcinoids ,7 Merkel cell carcinomas, 46 adrenal pheochromocytomas (37 sporadic an d9 familial), an d7 abdominal paragangliomas for loss of heterozygosity (LOH) and/or mutations at the SDHD gene locus. LOH was detected i n5 out o f8 (62%) informative midgut carcinoids, i n9 out of 30 (30%) sporadic pheochromocytomas, in none of the familial pheochromocytomas (0%), and in 1 out o f6 (17%) abdominal paragangliomas. No sequence variants were detected in the pheochromocytomas or paragangliomas. However, two constitutional putative missense mutations, H50R and G12S, were detected in two midgut carcinoids, which were both associated with LOH of the other allele. The same sequence variants were also detected in two Merkel cell carcinomas. In addition, the S68S polymorphism was found to coexist with the G12S sequence variant in both cases. In conclusion, we show that alterations of the SDHD gene seem to be involved in the tumorigenesis of both midgut carcinoids and Merkel cell carcinomas. © 2002 Wiley-Liss, Inc.

Prostate cancer is a highly common disease in the Western countries with its prevalence growing every year with the standard of living and life expectancy. Despite extensive studies prostate cancer presents still considerable challenges to patient care, scientists and societies. As still no curing treatment exists for the recurrent form of the disease prostate cancer is likely to remain an intensive subject for study also in the future. Even though numerous studies exists that try to characterize individual components and pathways of regulation, no real attempts have been made to characterize the regulation profile of prostate cancer in a genome-wide level. This thesis forms a basis for this ambitious feat by using computational methods in transcription factor mediated regulation prediction and network inference. DNase I hypersensitivity guided genome scanning with transcription factor specific position weight matrices is performed in several manners, producing a catalogue of putative regulation connections in LNCaP cells. The predicted connections are subjected to thorough evaluation and several applications of the first method are presented, forming a strong set of basic guidelines for computational prediction based regulome assembly for future studies. In addition, as a further application gene expression data is applied to selectively extract a subnetwork of regulation present exclusively in the studied LNCaP cells. As a conclusion the genome-wide computational regulome assembly is presented as a functional but challenged approach with enormous potential due to its possible applications as cell type or disease specific network profiling tool.

Particular boundary correlation functions of conformal field theory are needed to answer some questions related to random conformally invariant curves known as Schramm-Loewner evolutions (SLE). In this article, we introduce a correspondence and establish its fundamental properties, which are used in the companion articles [JJK16, KP16] for explicitly solving two such problems. The correspondence associates Coulomb gas type integrals to vectors in a tensor product representation of a quantum group, a q-deformation of the Lie algebra sl2. We show that desired properties of the functions are guaranteed by natural representation theoretical properties of the vectors., Comment: 51 pages, 7 figures; v5 (final): accepted for publication in JEMS

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Drawing on insights provided by linguistic anthropology, the study of multisemioticity and research in computer-mediated discourse (CMD), this chapter discusses how entextualization (Bauman & Briggs, 1990; Silverstein & Urban, 1996; Blommaert, 2005, pp. 46–8) and resemiotization (Iedema, 2003; Scollon & Scollon, 2004, pp. 101–3; Scollon, 2008) are key resources for identity work in social media. Three key arguments inspire and give direction to our discussion, each of them laying down touchstones for language scholars who wish to investigate identity in social media. First, for many individuals and social or cultural groups, social media are increasingly significant grassroots arenas for interaction and cultural activities (Androutsopoulos, 2011; Kytola, 2012a, 2012b; Leppanen, 2012; Peuronen, 2011) which overlap, complement and intertwine in different ways with their offline activities. Importantly, social media encompass a range of diverse formats for social action, interaction and performance; thus they can be ‘social’ in quite different ways (see Baym, 2011, pp. 6–12) and offer various kinds of affordances for, and constraints on, identity performance.

Carcinoid tumors are rare neuroendocrine tumors occurring in the lung or in the digestive tract where they are further subclassified as foregut, midgut, or hindgut carcinoids. To gain a better understanding of the genetic basis of the different types of carcinoid tumors, we have characterized numerical imbalances in a series of midgut carcinoids, and compared the results to previous findings in carcinoids from the lung. Numerical imbalances were revealed in 16 of the 18 tumors, and the most commonly detected aberrations were losses of 18q22-qter (67%), 11q22-q23 (33%), and 16q21-qter (22%), and gain of 4p14-qter (22%). The total number of alterations found in the metastases was significantly higher than in the primary tumors, indicating the accumulation of acquired genetic changes in the tumor progression. Losses of 18q and 11q were present both in primary tumors and metastases, whereas loss of 16q and gain of 4 were only detected in metastases. Furthermore, the pattern of comparative genomic hybridization alterations varied depending on the total number of detected alterations. Taken together, the findings would suggest a progression of numerical imbalances, in which loss of 18q and 11q represent early events, and loss of 16q and gain of 4p are late events in the tumor progression of midgut carcinoids. When compared to previously published comparative genomic hybridization abnormalities in lung carcinoids, loss of 11q was found to occur in both tumor types, whereas loss of 18q and 16q and gain of 4 were not revealed in lung carcinoids. The results indicate that inactivation of a putative tumor suppressor gene in 18q22-qter represents a frequent and early event that is specific for the development of midgut carcinoids.

Comparative genomic hybridization (CGH) studies have shown that chromosome 8 is a frequent target for chromosomal aberrations in breast cancer. We characterized these aberrations of chromosome 8 in 16 breast cancer cell lines (BT-474, BT-549, CAMA-1, DU-4475, MCF-7, MDA-MB-134, MDA-MB-157, MDA-MB-361, MDA-MB-415, MDA-MB-436, MPE600, SK-BR-3, T-47D, UACC-812, UACC-893 and ZR-75-1) by CGH, fluorescence in situ hybridization (FISH) with arm- and locus-specific probes, and spectral karyotyping (SKY). Chromosome 8 was structurally abnormal in 13 of 16 cell lines. Loss of 8p was detected in nine cell lines, gain of entire 8q in six cell lines, 8q21-qter in three, 8q23-qter in two, and 8q12-qter and 8p21-q21 in one cell line. Extra copies of the C-MYC oncogene were found in 11 cell lines, but high-level amplification only in SK-BR-3. Derivative chromosomes including material from chromosomes 8 were complex, and the breakpoints were strikingly dissimilar. Chromosome 11 was the most frequent translocation partner with chromosome 8 (in 7 cell lines). Isochromosomes and/or isoderivative 8q were found in four cell lines. The high frequency and complexity of alterations at 8q indicate a significant pathogenetic role in breast cancer. The high-level amplification of c-myc is less common than previously thought.

Editor—Multiple endocrine neoplasia type 1 (MEN 1, OMIM 131100) is transmitted as an autosomal dominant trait with an equal sex distribution and close to full penetrance. Hyperparathyroidism occurs in over 90% of the cases and is invariably associated with multiglandular disease. In addition, the patients may develop tumours of the endocrine pancreas, the anterior pituitary, and the adrenal cortex, as well as lipomas and carcinoids.1The MEN1 tumour suppressor gene at 11q13 was cloned by positional cloning and the protein, menin, has been found to bind specifically to JunD leading to inhibition of JunD activated transcription.2-5 Following the initial description of the disease gene, over 200 MEN1 germline mutations scattered throughout the entire gene have been reported. The majority of these mutations are unique and no clear cut genotype-phenotype correlation has been established so far.3 4 6-13 To date, only a few reports of a founder effect in MEN 1 families have been published.10 14 15 In all the cases, the evidence for a founder chromosome was based on the presence of a shared disease haplotype and a MEN1 mutation, in combination with a common geographical origin of the families involved. To date, more than 30 rare single gene diseases, mostly autosomal recessive, have been identified in the Finnish population.16 17 The clustering of mutations in the Finnish population can be explained by the mechanisms of isolation, genetic drift, and founder effect. The relatively small founder population, the geographical isolation, and the internal migration movement in the 1500s led to the formation of numerous founder populations. The Finnish population has been widely used in linkage disequilibrium studies for mapping disease gene loci. By combining genetic and clinical investigations with careful genealogical studies, several founder chromosomes for various genetic diseases have been established.17-19 …

Prostate cancer cell lines have been widely used as model systems characterizing pathogenetic, functional, and therapeutic aspects of prostate cancer development. However, their chromosomal compositions are poorly characterized. In this study, five prostate cancer cell lines-TSU-Pr1, JCA-1, NCI-H660, ALVA-31, and PPC-1-were investigated by G-banding, comparative genomic hybridization (CGH), and spectral karyotyping. The results were combined with our previous findings in the prostate cancer cell lines PC-3, DU145, and LNCaP. By comparative genomic hybridization (CGH), the most frequent losses were observed at 13q, 8p, 9p, and 4q, whereas gains were most commonly seen at 8q, 10q, and 18p. The composite karyotypes were characterized by multiple numerical and structural chromosomal aberrations. Recurrent breakpoints at 5q11, 8p11, and 10q22 were observed to participate in deletion and translocation events in five of the cell lines, suggesting the importance of tumor suppressor and/or oncogenes in these regions. ALVA-31 and PPC-1 shared nine identical derivative chromosomes, two of which have also been detected in PC-3. In addition, the identification of the same homozygous deletion at D10S541 and of an identical TP53 gene mutation in all three cell lines suggests a common origin of these cell lines.

Editor—Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is an autosomal dominant neurocutaneous disease characterised by cafe au lait spots and neurofibromas. The gene responsible for the disorder is located in the chromosome region 17q11.2. The prevalence of NF1 has been estimated to be about 1/3500 in the USA and the United Kingdom,1-3 and its birth incidence has been reported to vary from 1/25584to 1/4292,5 the mutation rate being 3.1 × 10–5 to 6.5 × 10–5. The first population based study of NF1 was performed in Sweden by Samuelsson6in 1981, who found 74 adult NF1 patients in the Gothenburg region, implying a prevalence of 1/4600. In 1989, Huson et al 4 discovered 135 NF1 patients in 69 families in south east Wales, 83 of whom were index cases and 52 affected relatives, with a prevalence of 1/4150. The highest estimated prevalence for NF1, 1/2190, has been reported in Dunedin, New Zealand, by Fuller et al ,7 who also showed that the prevalence peaked in the age group 20-29 years. A fourth report from north east Italy by Clementi et al 5 quoted a prevalence of 1/6711 and a very high mutation rate of 6.5 × 10–5 gametes per generation. The purpose of the present work was to determine the prevalence and genetic characteristics of NF1 in northern Finland, including a survey of first degree relatives of patients and linkage data, to assist in the diagnosis of affected subjects. Clinical data on the patients will be reported separately. The study was carried out between October 1989 and December 1996 in the region of Oulu University Hospital (OUH) in northern Finland with a total population of 733 037 (31 December 1996).8The basic material consisted of families …

Alterations of 3p are the most frequently observed changes in follicular thyroid carcinomas. Loss of 3p25-pter has been speculated to be a critical event in the malignant transformation of a subset of thyroid follicular neoplasms. The present report describes a minimally invasive follicular thyroid carcinoma (FTC) with a balanced t(3;7)(p25;q34) and dic(15;22)(p11;p11) as the only abnormalities. The alterations were present in all metaphases analyzed and were demonstrated by G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). This study represents the second case of FTC where 3p25 is involved in a balanced translocation. The findings support the existence of a gene locus in this region which is involved in the tumorigenesis of thyroid carcinoma.

This paper describes the development and a demanding field application of a double charge-coupled device (CCD) camera system, which allows simultaneous imaging at two different wavelength bands through common front-end optics. The imaging system has been assembled using two 1280 × 1024-pixel, 12-bit digital cameras together with standard, commercially available optical components for image splitting and filtering. The pixel resolution and wavelength separation of the system can be changed according to the requirements of the given application and the basic optical set-up can be used together with a variety of different types of front-end optics. The construction and performance of the double-camera system are described, together with preliminary experimental results from applying the system to in-cylinder combustion diagnostics of heavy-duty size-class, direct-injection diesel engines. To provide optical access into the combustion chamber of series-production-type engines, endoscope-based optics were used together with the camera system. Images taken at the two separate wavelength bands were used to calculate pyrometric diesel flame temperatures based on the blackbody radiation of the soot contained in the flame. The measurement system has been applied to engines with cylinder bores ranging from 20 cm up to 64 cm, delivering 0.15-1.6 MW power per cylinder during the measurements. In this paper specific results from measurements with Wartsila 4L20 and 6L32 engines are reported. These engines have 20 and 32 cm cylinder bores, respectively. In addition to the two-colour flame-temperature measurements, spectrally resolved measurements were performed to investigate a cloud-like, self-luminous phenomenon that was observed above the piston top even prior to the injection of fuel into these engines. This phenomenon was associated with the evaporating and chemically reacting fuel that originates from the residues which have been carried onto the piston top from the previous cycles. For the in-cylinder measurements reported here, the production-type test engines were only slightly modified to accept the endoscopic optics. During the measurements the engines were operated with realistic diesel fuels and other operation parameters. To the best of our knowledge, there have been no previous corresponding measurements reported in the literature for diesel engines of this size.

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN1 region, we have investigated the involvement of the MEN1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma.

Introduction: Plasma cell leukaemia is a rare disorder that usually carries an aggressive course with a rapidly fatal outcome. A variety of chromosomal abnormalities have been reported in plasma cell leukaemia but the clinical significance of an abnormal karyotype is still unclear. Materials and methods: We have applied the molecular cytogenetic techniques multicolour spectral karyotyping and microdissection in combination with fluorescence in situ hybridization on metaphases from a patient with primary plasma cell leukaemia and a fatal outcome. Results and conclusion: The chromosome analysis showed severe hypodiploidy and 12 marker chromosomes. Identification of the structural rearrangements was not possible using routine cytogenetic methods. Utilizing the methods above, all marker chromosomes could be identified in detail and the karyotype was shown to be very complex. Forty-three breakpoints were found, and 25 could be identified at the band level, among others 14q32 where the immunoglobulin heavy chain locus is situated. Thus, these techniques provide the opportunity to resolve very complex chromosomal changes in a way that has not been previously possible and will consequently be of great importance in the search for hot spots that may harbour new cancer genes. The Hematology Journal (2000) 1, 95‐101

Since meconium aspiration often induces an inflammatory respiratory disorder, we investigated the effects of intrapulmonary meconium on the expression of cyclooxygenase-1 and 2 in rat lungs. Suspension of human meconium was instilled intratracheally into ventilated lungs of anesthetized rats, while control rats received an equal volume of saline. The meconium lungs were ventilated either with air or 100% oxygen, and control lungs were ventilated with air. After 3 h, the lungs were removed and the amount of cyclooxygenase-1 and 2 mRNA was measured by Northern blot analysis. Cyclooxygenase-1 mRNA was clearly expressed in control rat lungs, while cyclooxygenase-2 expression was minimal. Meconium administration markedly upregulated the expression of cyclooxygenase-2 mRNA, while cyclooxygenase-1 expression remained unchanged. Increased expression of cyclooxygenase-2 was detected in rat lungs ventilated with either air or oxygen. Our data thus indicate that meconium aspiration induces pulmonary expression of cyclooxygenase-2, suggesting an important role for prostaglandins in the meconium aspiration-induced inflammation in neonatal lungs.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.

Primary hyperparathyroidism is a common endocrine disease that also occurs in a number of inherited disorders, including multiple endocrine neoplasia type 1 (MEN1). Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 has been found in 30% of sporadic parathyroid tumors, making the recently cloned MEN1 gene a prime candidate for involvement in parathyroid tumorigenesis. Using LOH and single strand conformation analysis, we screened 45 sporadic tumors from 40 patients for alterations involving the MEN1 gene. Thirteen tumors showed LOH at 11q13, and in 6 of these cases, somatic mutation of the MEN1 gene was detected. In tumors without LOH, no mutations were detected. The mutations consisted of 3 small deletions, 1 insertion, and 2 missense mutations that had not been reported in MEN1 patients or parathyroid tumors previously. Using messenger ribonucleic acid in situ hybridization, the expression of the MEN1 gene was studied. There was no difference in expression between normal and tumor tissu...

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

The European Consortium on MEN-1. The search for the MEN1 gene (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 441–6. The search for the gene whose mutations predispose individuals to multiple endocrine neoplasia type 1 (MEN-1) started in 1988 when the MEN1 locus was assigned to 11q13, close to PYGM. It came to an end with the recent identification of a gene expressed ubiquitously which harbours inactivating mutations associated with MEN-1. During these nine years, the genetic linkage interval had been slowly reduced, and losses of heterozygosity (LOH) in MEN-1 tumours had given strong indications that MEN1 was a tumour suppressor gene. It is ironic that MEN1 was finally found to be located less than 100 kb telomeric to PYGM. From the beginning, this gene was the most tightly linked genetically to MEN-1. In addition, LOH had already shown (in 1990) that it was the most likely centromeric boundary of the MEN1 minimal region. We recently narrowed the critical region to 900 kb through meiotic mapping, and established a 1200-kb sequence-ready contig consisting of cosmids, bacterial artificial chromosomes (BACs) and P1-derived artificial chromosomes (PACs), including three gene clusters (19 genes and 3 expressed sequence tags). Taking LOH results into account, the gene was likely to be present in the 300-kb area telomeric to PYGM that we had covered with BACs. One of the novel genes that we have identified by cDNA selection in this region, SCG2 (Suppressor Candidate Gene 2), proved to be identical to the recently published MEN1 gene. Mutation analysis of SCG2 in 11 unrelated MEN-1 families identified one nucleotide sequence polymorphism and 10 different mutations that segregated with the disease.

Background: Since the discovery of HIV, minimizing the use of donor blood has become increasingly important in surgical activity. In Finland, however, the use of homologous red blood has grown considerably during the past years. Therefore, we found it necessary to conduct a nationwide survey of transfusion practices in elective surgery. This report deals with transfusions in coronary artery bypass (CABG) operations in all Finnish cardiac centres. Methods: The study group comprised 804 primary CABG patients operated during a 2-year period. Two reviewers retrospectively examined the data concerning the use of and indications for homologous and autologous blood in the patient charts. Results: In all, 705 (88%) of patients received homologous blood. The proportions of patients receiving blood components differed between hospitals: from 53 to 99% for red cells, 2 to 22% for fresh frozen plasma and 5 to 49% for platelets. The variation was not caused by diverse patient populations: the mean number of blood component units transfused per patient differed from 1 to 6 between centres — even after adjustment for confounding variables. Multiple blood conservation methods were used in one centre. Nevertheless, homologous blood was administered to 88% of their patients. Conclusions: A considerable proportion of CABG patients are transfused with homologous blood in Finland compared to other countries. In addition, the transfusion practices proved highly variable between hospitals and were determined largely by local opinions. This study reveals a clear demand for prospective studies and constructive discussion among anaesthesiologists to establish uniform guidelines for blood use in cardiac surgery.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary. The MEN1 gene has been localised to a 2-Mb region of chromosome 11q13 by meiotic mapping studies in MEN1 families. Such studies may have a limited resolution of approximately 1 cM (i.e. 1 Mb) and we have therefore investigated 96 MEN1 families (40 British, 17 French, 12 Finnish, 7 Swedish, 7 Dutch, 7 North American, 2 Australian, 1 New Zealand, 1 German, 1 Spanish and 1 Danish) for linkage disequilibrium, in order to facilitate a finer mapping resolution. We have utilised five microsatellite DNA sequence polymorphisms from the candidate region and have accurately determined their allele sizes, which ranged from 161 bp to 272 bp. The heterozygosity and number of alleles (given in brackets), respectively, at the loci were: D11S1883 (76%, 11), D11S457 (55%, 5), PYGM (94%, 18), D11S1783 (10%, 4) and D11S449 (87%, 16). Allelic association was assessed by Chi-square 2 x n contingency tables, by Fisher exact 2 x n contingency tables and by a likelihood-based approach. The results of haplotype analysis revealed 91 different affected haplotypes in the 96 families, an identical affected haplotype being observed in no more than two families. These results indicate the absence of an ancestral affected haplotype. Significant linkage disequilibrium (P < 0.005) could be established amongst the microsatellite loci but not between the loci and MEN1 in either the total population or in any of the geographical sub-populations, The absence of linkage disequilibrium between MEN1 and the polymorphic loci is probably the result of the occurrence of multiple different disease-causing mutations in MEN1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a

Cancer diseases are treated with targeted drugs utilizing several distinct mechanisms of action. The decision about targeted therapy will result from multiprofessional collaboration based on a representative biopsy, precise morphological diagnosis, elucidation of the extent of the disease and reliable methods of molecular analysis. Changes at the molecular level are determined by immunohistochemical stainings indicating the expression of proteins and by cytogenetic and molecular genetic tests. When successful, the clinical decision provides the cancer patient with maximally effective therapy and guarantees that the patient will not be needlessly exposed to ineffective treatment involving side effects.

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) accounting for 2% to 4% of all non-Hodgkin lymphomas. We report a family of 3 siblings with PMBCL and their cousin with extranodal DLBCL. The histopathological characteristics of lymphomas of all 4 patients are similar, implying post-germinal center differentiation and growth deregulation by other mechanisms than BCL2-mediated inhibition of apoptosis and suggesting a shared biological background. We aimed to identify the genetic defect underlying lymphoma susceptibility in this family using exome sequencing and linkage analysis. The only variant segregating in all 4 patients and not reported in genetic databases was 5533C>A (His1845Asn) in the MLL gene. To our knowledge, this is the first time when familial clustering of PMBCL is reported. Although we propose MLL as a candidate predisposition gene for this condition, this finding needs to be validated in additional cases.

We study the probabilities with which chordal Schramm-Loewner Evolutions (SLE) visit small neighborhoods of boundary points. We find formulas for general chordal SLE boundary visiting probability amplitudes, also known as SLE boundary zig-zags or order refined SLE multi-point Green's functions on the boundary. Remarkably, an exact answer can be found to this important SLE question for an arbitrarily large number of marked points. The main technique employed is a spin chain-Coulomb gas correspondence between tensor product representations of a quantum group and functions given by Dotsenko-Fateev type integrals. We show how to express these integral formulas in terms of regularized real integrals, and we discuss their numerical evaluation. The results are universal in the sense that apart from an overall multiplicative constant the same formula gives the amplitude for many different formulations of the SLE boundary visit problem. The formula also applies to renormalized boundary visit probabilities for interfaces in critical lattice models of statistical mechanics: we compare the results with numerical simulations of percolation, loop-erased random walk, and Fortuin-Kasteleyn random cluster models at Q=2 and Q=3, and find good agreement., Comment: 59 pages, 14 figures. v3: minor corrections, references updated, to appear in Annales Henri Poincare

Tässä tutkimuksessa tarkasteltiin refleksiivisyyden kehittymisen prosessia parisuhdeväkivallan hoitoon tarkoitetussa pariterapiassa. Refleksiivisyys on kognitiivis-konstruktiivisen teorian käsite, jolla viitataan yksilön kykyyn tiedostaa ja säädellä omaa ajatteluaan ja käyttäytymistään. Tutkimuksessa pyrittiin selvittämään, muuttuuko yksilöiden väkivaltaongelman käsittely refleksiivisemmäksi pariterapian aikana sekä onko kehitys samanlaista parin molemmilla osapuolilla. Tutkimus oli osa Pariterapia parisuhdeväkivallan ehkäisemisen keinona -projektia. Tässä tutkimuksessa aineistona toimi kolmen parin kestoltaan eri pituiset terapiaprosessit, joista tarkasteltiin yhteensä 33 terapiaistuntoa. Näistä istunnoista 21 oli paritapaamisia, kahdeksan miehen ja neljä naisen yksilötapaamista. Keskimääräinen tapaamisen kesto oli 1,5 tuntia. Aineiston analysoinnissa menetelmänä oli laadullinen sisällönanalyysi, jonka avulla tutkittavien puhetta luokiteltiin viiden refleksiivisyyden tason perusteella. Tulokset osoittivat, että väkivaltaongelman käsittelyyn liittyvä refleksiivisyyden kehittyminen oli saman parin osapuolilla pääosin samanlaista, mutta parien välillä vaihtelevaa. Terapiaprosessien aikana yhdellä parilla refleksiivisyys kehittyi myönteiseen suuntaan, yhdellä parilla se eteni huonompaan suuntaan, ja yhdellä parilla pysyi samalla tasolla. Keskeisiä tekijöitä refleksiivisyyden korkeammalle tasolle kehittymisen kannalta olivat luottamuksen saavuttaminen kumppaniin sekä väkivaltatilanteisiin liittyvän oman osuuden ja rajojen tiedostaminen. Kielteisen muutokseen tai muuttumattomaan refleksiivisyyden tason taustalla olivat oman osuuden tiedostamisen vaikeus väkivaltatilanteissa sekä kielteisten tunteiden ilmaiseminen ilman niiden prosessointia. Myös epävarmuus parisuhteen tulevaisuudesta sekä vaikeus tehdä sitä koskevia päätöksiä liittyivät kielteiseen muutokseen. Tämän tutkimuksen perusteella voidaan todeta, että kognitiiviskonstruktiivinen teoria ja refleksiivisyyden käsite tarjoavat hyödyllisen näkökulman pariterapiassa tapahtuvan muutoksen tutkimiseen parisuhdeväkivallan hoidossa. This thesis examines the process of reflexivity in couples therapy in the context of intimate partner violence. Reflexivity is a concept of the cognitive-constructive theory. It refers to an individual’s ability to become aware of and regulate her/his own thinking and behavior. The thesis aims at finding out whether the processing of intimate partner violence changes during the couples therapy, and whether the development is similar in both parties of the couple. This study is a part of the project “Research on couple treatment in intimate partner violence”. The data of this thesis consist of three heterosexual couples’ therapy processes with different durations. In total, 33 therapy sessions were examined. 21 of these were couple sessions, eight were the man’s individual sessions and four were the woman’s individual sessions. The average duration of one meeting was 90 minutes. The method used for the study was content analysis, and the speech of the participants was classified in five categories of reflexive functioning. The results show that the development of reflexivity related to the processing of intimate partner violence was mainly similar in both parties of each couple, but varied considerably between couples. During the therapy processes, reflexivity developed in a positive direction with one couple, in a negative direction with one couple and remained on the same level with one couple. The main factors contributing to the development of reflexivity on a higher level were gaining confidence with the partner, and becoming aware of one’s responsibility and one’s limits related to violent situations. The factors related to the negative change or no change in the development of the reflexivity were difficulties in becoming aware of one’s responsibility related to violent situations, and the expression of negative emotions without processing them. Insecurity regarding the future of the relationship and difficulties in decision-making in this area also correlated with the negative change. Based on this study, it is argued that the cognitive-constructive theory and the concept of reflexivity provide a useful point of view for the examination of change in couples therapy in the treatment of intimate partner violence.

The architecture of automotive systems is currently changing from a number of local, more or less isolated electronics to a functionally integrated distributed system which is linked by a network. This disengagement from local implementations is the platform for innovative control approaches in vehicles. It is supported by enhancements in microcontroller capabilities, due to the introduction of operating systems, co-processing, more efficient development process and by the application of artificial intelligence into automotive systems.

Paroxetine, like other SSRIs, is reported not to increase the number of malformations in infants exposed to these drugs in utero. However, late pregnancy exposure to SSRIs sometimes leads to perinatal complications resembling the symptoms seen in serotonergic overstimulation. We report here a case of third trimester paroxetine exposure with adverse birth outcome in a newborn. The clinical symptoms in the infant included severe tremor and rigidity as well as loose stools during the first 4 days of life. Plasma paroxetine concentrations in infant plasma were quite low after birth, but she was genotyped to be a poor metabolizer of CYP2D6, the enzyme catalyzing the metabolism of paroxetine. In accordance with an earlier report, we suggest that even low plasma concentrations of paroxetine may be related to perinatal complications in infants exposed to paroxetine during late pregnancy and that the poor metabolizer genotype of CYP2D6 may be a risk factor for these complications.

Syftet med denna studie är att skapa en ökad förståelse för hur Kinas aktiemarknad ser ut, genom att i huvudsak analysera landets största börs Shanghai Stock Exchange. En analys av marknaden har gjorts där vi studerat asymmetrisk information på Kinas aktiemarknad och studerat ifall det påverkar marknadseffektiviteten.

While the previous chapters in this volume have dealt with more institutionally constructed language-ideological discourses, this chapter shifts the lens to language ideologies at play on a markedly ‘grassroots’ level of language use. The sociocultural and technological context of this chapter is interactive, multi-authored discussion forums of the web that allow participants an extent of anonymity. Web forums are a distinctive format of computer-mediated discourse (CMD), most often a discourse domain with little institutional control, and thus relatively free of high-modernist constraints and demands for ‘purity’ of language use. Instead, late-modern hybridity, freedom of stylized expression, and identity play enable a different order of peer regulation and normativity, on which this chapter aims at opening a conceptual and empirical window.