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Most studies concerning therapy and prognosis in diffuse large B-cell lymphoma (DLBCL) are based on highly selected patient material. To evaluate treatment, clinical prognostic factors, and outcome in a population-based cohort, we performed a retrospective study comprising 535 de novo DLBCL patients in western Sweden, diagnosed between 1995 and 2000. The median age was 73 years. Treatment with a curative intent was administered to 376 (70%) patients. The International Prognostic Index (IPI) strongly predicted overall (OS) and progression-free (PFS) survival, but high age (68 vsor = 68 years) had no significant influence on response rate (p = 0.86) or PFS (p = 0.14). Male sex had a negative impact on both OS (p0.001) and PFS (p0.001), independent of IPI. In conclusion, a considerable proportion of the patients did not receive curative treatment, but among those treated, the response and PFS were not influenced by age. As men had lower PFS and OS than women, it seems important that gender perspective be taken into account in future studies.

Bertrand supergames with non-binding communication are used to study price formation and stability of collusive agreements on experimental duopoly markets. The experimental design consists of three treatments with different costs of communication: zero-cost, low-cost and high-cost. Prices are found to be significantly higher when communication is costly. Moreover, costly communication decreases the number of messages, but more importantly, it enhances the stability of collusive agreements. McCutcheon (1997) presents an interesting application to antitrust policy by letting the cost of communication symbolize the presence of an antitrust law that prohibits firms from discussing prices. Although our experimental results do not support the mechanism of McCutcheon's (1997) argument, the findings point in the direction of her prediction that antitrust laws might work in the interest of firms.

In this work, circuits for on-chip measurement and periodic waveform capture are designed. The aim is to analyze disturbances in mixed-signal chips such as simultaneous switching noise and the transfer of substrate noise. A programmable reference generator that replaces the standard digital-to-analog converter is proposed. It is based on a resistor string that is connected in a circular structure. A feature is that the reference outputs to the different comparators in the measurement channels are distributed over the nodes of the resistor string. Comparing with using a complete digital-to-analog converter, the use of a buffer is avoided. Hence, there is a potential reduction in the parasitic capacitance and power consumption as well as an increase in speed. We present results from a test chip demonstrating that simultaneous switching noise can be measured with the presented approach.

One of the major contributors to the static nonlinearity of a current-steering digital-to-analog converter (DAC) is mismatch between current sources. A technique for enhancing the yield of binary-weighted current-steering DACs is proposed. The technique utilizes a special case of a general technique for spectral shaping of DAC nonlinearity errors presented earlier and requires oversampling. The technique relies on two DAC models with low computational complexity that can be integrated with the DAC at a negligible cost in terms of area and power consumption. Behavioral-level simulation results indicate that the proposed method has a good potential of enhancing the yield of binary-weighted DACs for situations where the matching errors constitute the dominating source of nonlinearity.

Immune surveillance of tumours is mediated by cytotoxic T cells (CTL) that recognise tumour antigen. Reduced reactivity of CTL towards tumour cells could thus lead to disease progression and loss of tumour control. In B-cell chronic lymphocytic leukaemia (B-CLL), the function of tumour-reactive CTL seems to correlate inversely to disease stage. Inhibitory NK cell receptors are known to suppress the CTL response upon interaction with major histocompatibility complex (MHC) class I and increased expression of such receptors on CTL may inhibit the anti-tumour response. So, the aim of this study was to investigate the expression of NK cell inhibitory receptors on CTL in B-CLL patients and if such expression correlated to disease stage. CD8+ T cells from B-CLL patients in Binet stage A (n = 26) and stage C (n = 14) and healthy controls (n = 14) were analysed for the expression of killer immunoglobulin-like receptors (KIR) CD158a (KIR2DL1), CD158b (KIR2DL2), CD158e (KIR3DL1) and the C-type lectin receptor CD94, by flow cytometry analysis. Patients with advanced disease (Binet stage C) had a significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than patients with non-progressive disease (Binet stage A) and healthy controls. Stage C patients also had a significantly higher percentage of CTL expressing CD158a than stage A patients. No statistically significant differences were found between Binet A patients and healthy controls. Our results suggest that increased expression of KIR and CD94 on CTL in advanced stage B-CLL may potentially contribute to the impaired anti-tumour immune response in these patients.

Introduction: The addition of the anti-CD20 antibodies rituximab or ofatumumab to chemotherapy has improved the outcome for patients with chronic lymphocytic leukemia (CLL), but the efficacy of anti-CD20 monoclonal antibodies (mAbs) as single agents is limited. Immunosuppressive reactive oxygen species (ROS), produced by myeloid cells, including monocytes, may be a limiting factor for the efficacy of ADCC-dependent therapy. With the aim of reducing a potentially inhibitory role of ROS on mAb-dependent NK cell cytotoxicity against CLL cells, we performed in vitro cytotoxicity experiments in the presence of monocytes and the ROS formation inhibitor histamine dihydrochloride (HDC). Methods: After informed consent, blood samples were collected from Binet stage A CLL patients seen at Sahlgrenska University Hospital, Gothenburg, Sweden. NK cells, monocytes and CLL cells were isolated from PBMCs by immunomagnetic negative selection or flow cytometry. ROS production by monocytes was assessed by isoluminol-enhanced chemiluminescense upon stimulation with the chemotactic peptide fMLF in the presence or absence of CLL cells, rituximab (Roche), ofatumumab (GSK), HDC or the NADPH oxidase inhibitor DPI. NK cell death was assessed by flow cytometry after over-night culture of monocytes and lymphocytes. Autologous ADCC assays were performed with NK cells, monocytes and CFSE-labeled CLL cells in the presence or absence of rituximab, ofatumumab, HDC, catalase and interleukin-2 (IL-2). CLL cell death was determined by flow cytometry after live/dead staining. The study was approved by the local ethical review board of Gothenburg, and conducted in accordance with the declaration of Helsinki. Results: Rituximab and ofatumumab both triggered extracellular ROS production by monocytes. ROS production was blocked by the NADPH oxidase inhibitor DPI. Furthermore, monocytes induced ROS-dependent apoptosis in adjacent NK cells. In the cytotoxicity experiments, rituximab-mediated NK cell dependent cytotoxicity against CLL cells was significantly inhibited by the presence of autologous monocytes. This suppression, as well as the induction of NK cell apoptosis, were dependent on ROS, since both HDC and catalase significantly increased cytotoxicity and rescued NK cells from monocyte-induced apoptosis. Expectedly, IL-2 augmented NK cell-mediated ADCC. Conclusion: The results imply that CLL patients harbor immunosuppressive myeloid cells that reduce CD20-antibody dependent NK cell-mediated cytotoxicity against leukemic cells by producing ROS. We propose that treatment with HDC, preferably in conjunction with NK cell stimulatory cytokines, may improve anti-CD20-based immunotherapy in CLL. Disclosures No relevant conflicts of interest to declare.

OFA was approved for the treatment of fludarabine and alemtuzumab refractory CLL on the basis of a single-arm study which also included pts with BFR CLL. This open label, randomized, Phase III study of OFA or PC treatment in pts with CLL refractory to fludarabine and with bulky lymphadenopathy (at least one lymph node > 5 cm) was conducted to confirm the results of OFA in BFR pts and also through a 2nd randomization to compare extended OFA (12 months) vs. approved regimen of OFA (6 months). PC was considered an appropriate comparator for these pts given the lack of a consensus around standard of care treatment for this difficult-to-treat population. Pts were randomized 2:1 to receive either the approved regimen of 8 weekly infusions of OFA followed by 4 monthly infusions (Dose 1, 300 mg; Doses 2–12, 2000 mg) or PC of non-OFA containing therapy, including treatments approved for CLL and well established standards of care for up to 6 months. Pts in the OFA arm who had an investigator-assessed CR, PR or SD underwent a 2nd 2:1 randomization to 6 additional OFA infusions 2000 mg every 4 weeks (OFA Ext), or observation (Obs). Pts in the PC arm who developed disease progression during the study could receive OFA salvage therapy for up to 12 months of treatment. Premedication for OFA infusions consisted of glucocorticoid, paracetamol, and antihistamine. The primary objective of this study was to evaluate progression-free survival (PFS) with OFA treatment versus PC as assessed by an Independent Review Committee (IRC). Response assessments were performed using the 2008 Update of the NCI-WG CLL Guidelines [Hallek, 2008]. Secondary endpoints included overall response rate (ORR), time to next therapy (TNT), overall survival (OS), and safety. 122 pts were randomized (79 OFA, 43 PC). Pts completed a median of 12 OFA infusions and 3 months PC therapy. The median PFS (mPFS) as measured by IRC was 5.4 months for OFA and 3.6 months for PC (hazard ratio [HR] 0.79, p=0.27, stratified log rank test; Fig 1). Median PFS as assessed by the investigator (INV) was 7.0 months for OFA and 4.5 months for PC (HR 0.56, p=0.003). The median time to start of next anti-CLL treatment was 11.5 months for OFA and 6.5 months for PC (p=0.0004, stratified log rank test). The ORR (95% CI) by IRC evaluation was 38% (27%, 50%) for OFA and 16% (7%, 31%) for PC (p=0.02). 37 pts underwent a 2nd randomization to either OFA Ext (n=24) or Obs (n=13). From 2nd randomization, mPFS (INV) was 5.6 months for OFA Ext and 3.5 months for Obs (HR: 0.49, p=0.026, stratified log rank test) (Fig 2). Grade ³3 infusion reactions occurred in 5% of pts in the OFA arm with no fatal reactions in either arm. Grade ≥3 cytopenias in the OFA arm included neutropenia (24%, no prolonged neutropenia and 1 patient with late onset neutropenia), thrombocytopenia (8%), anemia (8%). Of the 43 PC pts, 22 received OFA Salvage with an ORR of 50% and mPFS of 5.4 months. Table of Response and Time to event Endpoints OFA (N=79) PC (N=43) Characteristics Median (range) Age, years 61.5 (46 – 82) 63 (40 – 76) No. prior therapies 4 (2 – 16) 3 (2 – 11) No. of infusions 12 (1 – 18) 3 (1 – 6) IRC Investigator Efficacy endpoints OFA PC p-value OFA PC p-value Responders, % 38% 16% 0.019 49% 37% 0.415 mPFS, months 5.36 3.61 0.267 7 4.5 0.003 OFA PC TNT, months 11.5 6.5 p=0.0004 OS, months 19.2 14.5 p=0.13 Figure 1. Kaplan-Meier Estimates of PFS by IRC (OFA vs. PC) Figure 1. Kaplan-Meier Estimates of PFS by IRC (OFA vs. PC) Figure 2. Kaplan-Meier Estimates of PFS by INV (OFA Ext vs. Obs from 2nd randomization) Figure 2. Kaplan-Meier Estimates of PFS by INV (OFA Ext vs. Obs from 2nd randomization) Conclusions: Although the study did not meet its primary endpoint of demonstrating statistically significant superior PFS by IRC, the ORR, PFS by investigator, TNT, and OS favor OFA and were consistent with previously reported results in BFR pts. There was also a longer PFS in pts who underwent the 2nd randomization to receive OFA Ext vs. the approved OFA treatment regimen of 6 months treatment. Disclosures Österborg: GSK: Research Funding. Off Label Use: Discussion of extended ofatumumab dosing (12 months) in addition to the approved 6 month dosing of ofatumumab in refractory CLL. Zaritskey:Novartis: Consultancy, Honoraria. Kaplan:GSK: Honoraria. Steurer:GSK: Consultancy, Honoraria, Research Funding. Schuh:GSK: Honoraria; Roche: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Napp: Honoraria. Montillo:GSK: Honoraria. Kulyaba:GSK: Honoraria. Gorczyca:GSK: Employment. Daly:GSK: Employment. Chai-Ni:GSK: Employment. Lisby:Genmab: Employment. Gupta:GSK: Employment.

In this study, we continuously monitored, second-by-second, concentration changes of two different carbohydrates (maltose and panose) by using monoclonal antibodies in an optical immunosensor based on total internal reflection fluorescence. Earlier studies have demonstrated that these antibodies increase their intrinsic tryptophan fluorescence upon binding of carbohydrate antigens. Using the four immobilized monoclonal antibodies with low affinities (K(d)10(-6)M), fast kinetics (k(off)1s(-1)), and high reversibility gave opportunities for developing a continuous immunosensor without any need for regeneration. Since intrinsic fluorescence was used, no extrinsic labeling was necessary. Sensitivity was in the range of 1-5 microM for panose, and 10-15 microM for maltose and the loss of intensity was as low as 3.5% per hour during measurements. Calculations of DeltaH degrees and DeltaS degrees from the temperature dependence of K(d) indicated an enthalpic driven antigen-antibody binding event that is diminished upon antibody immobilization. We feel certain that weakly interacting antibodies can be used in future applications for continuous monitoring where there is a need to achieve instantaneous information on the concentration of an analyte.

SummaryIdiopathic thrombocytopenic purpura (ITP) is an organ specific autoimmune disorder in whichT-lymphocyte abnormalities have pathogenetic importance.In a DNA microarray screen of CD3+ T-lymphocytes from ITP patients and healthy controls we found an altered expression of genes associated with apoptosis, e.g. A20, caspase-8 and Bax.This together with our previous findings of increased gene expression of Fas,interferon-g and IL-2 receptor beta (IL2RB) indicated an altered activation induced cell death (AICD) of T-cells in ITP. Using a proliferation assay we found that CD3+ lymphocytes from ITP patients were significantly more resistant to dexamethasone induced suppression compared to normal lymphocytes.We also found that cultured CD3+ lymphocytes from ITP patients in remission were more susceptible to apoptosis both in the presence and absence of dexamethasone compared to cells from patient with active ITP and healthy controls, as indicated by increased staining of AnnexinV binding. Our findings suggest that apoptotic resistance of activated T-lymphocytes in patients with active ITP may lead to defective clearance of autoreactive T-lymphocytes through AICD, which might cause a continued immune destruction of platelets. Conversely, a loss of resistance to AICD in ITP patients in remission might be an important mechanism for the achievement of remission.

Chronic idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder in which platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies. However, it is becoming clear that the pivotal process of the humoral immune response in the pathogenesis of the disorder is a complex interaction between antigen-presenting cells, T cells and B cells. Furthermore, it is increasingly evident that regulatory T cells play an important role and that T-cell-mediated cytotoxicity contributes to the destruction of platelets in ITP. Different new approaches to immunotherapy in chronic ITP have been explored, including use of anti-CD20, anti-CD154 and anti-CD52 antibodies. So far, these therapies have been antigen-nonspecific and the risk of general immunosuppression is a concern. Thus, improving our understanding of the interaction and relative contribution of humoral and cell-mediated mechanisms is essential for developing antigen-specific immunotherapies for the treatment of this disorder. This review aims to elucidate the current status of knowledge of the cellular and humoral immune components of chronic ITP, together with the implications of this knowledge for therapy.

Chronic idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder that is characterized by increased platelet destruction and is believed to be autoantibody mediated. In this study, CD3+ T cells from ITP patients had increased expression of genes involved in cell-mediated cytotoxicity. In addition, cytotoxic cell-mediated lysis of autologous platelets was shown in active ITP. Our data suggest that T-cell-mediated cytotoxicity is an alternative mechanism for platelet destruction in ITP.

Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK + anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was hot possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL.

The group of Soft Magnetic Composites (SMCs) have relatively recently expanded by the introduction of new materials with significantly improved low-medium frequency properties, which has made SMCs a viable alternative to steel laminations in a range of new applications, such as rotating machinery, sensors and fast switching solenoids. SMC components are successfully manufactured using the powder metallurgy compaction process. The isotropic nature of the SMC combined with the unique shaping possibilities opens up for 3D-design solutions. If carefully implemented advantages such as better performance, reduced size and weight, fewer parts and lower cost can be obtained. In this paper the SMC concept is presented i.e. the materials, part manufacturing and electromagnetic design. Possibilities and also limitations for SMC's are highlighted, prototype motors are described and finally some examples of commercial products are presented.

Post-hoc worknotes is a concept demonstration, an envisionment showing how workgroup communication could be supported using a combination of existing technologies in the field of nontextual information management. We have identified a number of use-driven requirements for video content management, including the tailoring of metadata structures to project and process models.

We present a patient with a Philadelphia chromosome positive (Ph+) acute lymphocytic leukaemia (ALL) refractory to standard induction chemotherapy. Treatment with the ABL-specific tyrosine kinase inhibitor STI571 (Glivec, Gleevec, imatinib mesylate) resulted in a complete haematologic and cytogenetic remission. Allogeneic stem cell transplantation from an unrelated donor could be undertaken while the patient was in STI571-induced complete remission from the leukaemia. At present, the patient has a 15-month post-transplantation follow-up and is in stable molecular remission as evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for the BCR/ABL fusion gene transcript. Our case demonstrates that STI571 can act as a bridge to potentially curative allogeneic stem cell transplant in otherwise poor prognosis Ph+ ALL.

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which activated T-helper (Th) cells and different Th-cell cytokines might play an important role. We have recently reported that chronic ITP patients in remission had elevated plasma levels of the Th3 cytokine transforming growth factor-beta1 (TGF-beta1), possibly as a part of a bystander immune suppression. In the present study we found that, in ITP patients with active disease [platelet count (plc)50 x 10(9)/l], mitogen-stimulated peripheral blood mononuclear cells (PBMC) had a significantly reduced production of TGF-beta1 (444 +/- 178 pg/ml; n = 6) compared with patients with plc 50-150 x 10(9)/l (1293 +/- 374 pg/ml; n = 9; P0.05), patients with plc150 x 10(9)/l (1894 +/- 244 pg/ml; n =12; P0.005) and healthy controls (1698 +/- 241 pg/ml; n = 10; P0.01). Nineteen per cent of ITP patients expressed a platelet-induced PBMC proliferation. Surprisingly, 22% of the ITP patients had a PBMC proliferation below the normal range, i.e. a suppressed proliferation in the presence of platelets; five of these six patients had active disease. In summary, this study demonstrated that chronic ITP patients with active disease had reduced PBMC production of the Th3 cytokine TGF-beta1. This result gives further support to the theory that chronic ITP in active phase is associated with a downregulated Th3-response.

Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping.To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting.Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ).Infants were randomized to DCC (≥180 seconds after delivery) or ECC (≤10 seconds after delivery).The main outcome was iron status at age 12 months; the secondary outcome was ASQ score.In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P = .40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P = .42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P = .04 for the interaction term).Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01245296.

Background: Filamentous bacteriophage are used as general cloning vectors as well as phage display vectors in order to study ligand–receptor interactions. Exposure to biphasic chloroform–water interface leads to specific contraction of phage, to non-infective I- or S-forms. Results: Upon exposure, phage were inactivated (non-infective) at methanol, ethanol and 1-propanol concentrations inversely dependent upon alcohol hydrophobicity. Infectivity loss of phage at certain concentrations of 1-propanol or ethanol coincided with changes in the spectral properties of the f1 virion in ultraviolet fluorescence and circular dichroism studies. Conclusions: The alcohols inactivate filamentous phage by a general mechanism – solvation of coat protein – thereby disrupting the capsid in a manner quite different from the previously reported I- and S-forms. The infectivity retention of phagemid pG8H6 in 99% acetonitrile and the relatively high general solvent resistance of the phage strains studied here open up the possibility of employing phage display in non-aqueous media.

Between 1989 and 1998 93 patients with malignant lymphoma were treated, in our centre, with high-dose chemotherapy and autologous stem cell transplantation. Diagnosis according to the REAL-classification were: 38 patients with high-grade lymphoma (diffuse large B-cell lymphoma (DLCL) (n = 26), anaplastic T-cell (n = 5), lymfoblastic (n = 3) and others (n = 4)), 31 patients with low-grade lymphoma (follicular (n = 18), mantle cell (n = 4), B-CLL (n = 3) and others (n = 6)) and, finally, 24 patients with Hodgkin's disease. The source of stem cells was bone marrow (14 patients), peripheral blood stem cells (64 patients) or a combination of both sources (15 patients). There was no early ( < 100 days) transplant-related mortality. One patient died 11 months post-transplant in unexplained liver failure and all other causes of death were related to relapse of lymphoma. So far, no case of myelodysplastic syndromes or secondary acute leukacmia's has occurred. Overall survival (OS) and progression-free survival (PFS) are: (a) DLCL (26 patients, 4-year probability) OS 40%. PFS 33%; (b) follicular (18 patients, 3-year probability) OS 79%, PFS 52%; (c) Hodgkin's lymphoma (24 patients, 5-year probability) OS 65%, PFS 55%. Out of 52 evaluable patients, 34 (65%) have reached remission inversion. The most important findings are no early transplantation-related mortality, remission inversion in a majority of patients, and so far no cases of secondary myelodysplastic syndromes (MDS) acute myelogenous leukaemias (AML). Concerning OS and PFS, our results seem to be in accordance with other centres.

We have used a novel microfluidic compact disk (CD) device for integration with diffractive optical elements (DOEs). The purpose of the DOEs is to reduce the amount of any external optics, as well as to enhance the system performance.

Studies performed in rabbit and mouse models and in a limited number of human subjects, show that transfused platelets bind thrombopoietin (TPO) and decrease its concentration in the circulation. The aim of the present study was to further examine this relationship. The material comprised 12 patients receiving a total of 21 transfusions, as part of the routine clinical treatment. Blood samples were collected from the patients immediately before and 30 min after completion of the platelet transfusion, and the corrected platelet count increment (CCI) was calculated. A commercially available ELISA kit was used to determine plasma TPO concentrations. Statistically significant reductions in median TPO concentration were observed in response to the platelet transfusions. Patients who were refractory to platelet transfusions showed the slightest decrease in TPO concentration. As for the linear regression between change in TPO level and CCI, only borderline significance was observed. Thus, our findings support the concept that platelets can remove TPO from the circulation.

Blastic transformation of essential thrombocythemia (ET) preceded by chemotherapy is occasionally described in the literature. In ET as well as in other myeloproliferative disorders the leukemogenic effect of alkylating agents and (32)P is well established, and recent reports also indicate a certain leukemogenic effect of hydroxyurea in these disorders. However, leukemic transformation in untreated ET seems to be a rare event. This is probably due to the fact that, at some time during their clinical course, most ET patients receive chemotherapy and are thereby exposed to leukemogenic challenge. We report on a woman with ET who had not received cytoreductive treatment prior to the development of acute myeloid leukemia, indicating that this transformation was a natural progression of her disorder.

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

Stockelberg D, Andersson P-O, Bjornsson E, Bjork S, Wadenvik H (Sahlgrenska University Hospital, Goteborg University, Goteborg, Sweden) Plasma thrombopoietin levels in liver cirrhosis and kidney failure (Review). J Intern Med 1999; 246: 471–475. Background. Recently, c-Mpl ligand (thrombopoietin, TPO) has been cloned by several groups and found to be a primary regulator of thrombopoiesis. Its mRNA expression has been detected in several organs including kidneys, bone marrow stroma cells, muscles, and is very strongly expressed in the liver. Objective. To clarify thrombopoiesis and the regulation of TPO in severe liver and renal failure. Design. We analysed plasma TPO levels in patients with biopsy verified liver cirrhosis (n = 18; mean platelet count 115 ± 54 × 109 L–1), in patients on chronic haemodialysis as a result of end-stage renal failure (n = 20; mean platelet count 295 ± 94 × 109 L–1), and in healthy individuals (n = 20; mean platelet count 250 ± 40 × 109 L–1). Plasma was prepared from EDTA-anticoagulated whole blood and a commercially available ELISA kit was used for the analysis. Results. The mean plasma TPO concentration amongst the normal individuals was 50 ± 14 pg mL–1. In the patients with liver cirrhosis and in patients on haemodialysis the mean TPO levels were 62 ± 19 pg mL–1 and 46 ± 17 pg mL–1, respectively. The mean plasma TPO concentration for the cirrhotic patients was significantly higher than the mean recorded for the healthy volunteers (P = 0.031), whereas no statistically significant differences in plasma TPO were seen between the group of end-stage renal failure and normals. Conclusion. Our results suggest that TPO production is maintained in liver cirrhosis and in renal failure, and that the thrombocytopenia in liver cirrhosis is not due to an impaired TPO production.

SummaryTo find if there is a relation between levels of haemostatic variables at low and high hormonal levels (oestradiol and progesterone) in an individual, blood samples were drawn from 12 women repeatedly during one menstrual cycle (Study I) and from 14 women undergoing in vitro fertilization, before hormonal stimulation and daily during the periovu- latory period (Study II). Regression coefficients were calculated between minimum (independent) and maximum (dependent) values in both studies. In Study II highly significant regression coefficients were found between oestradiol minimum (pretreatment) and maximum (mcdian 105 and 4730 pmol/1, respectively) for coagulation factors FVIII, von Willebrand Factor (antigen), FVII (activity and antigen), fibrinogen, protein C, protein S (free), antithrombin, plasminogen and plasminogen activator inhibitor-1; furthermore, between progesterone-minimum at day -3 or -2 (related to ovum pick up) and maximum (median 4.7 and 98 nmol/1, respectively) for FVIII, von Willebrand Factor, FVII (activity and antigen), protein C, protein S (free), and plasminogen. In Study I, where much lower hormonal levels were obtained at maximum (oestradiol median 297 pmol/1 and and progesterone 47 nmol/1), the same pattern was observed especially for FVIII, FX, fibrinogen, plasminogen and plasmin inhibitor. Thus, the concentration of a haemostatic variable at a low oestradiol or progesterone level can predict the level at a high hormonal level.

Background Delayed cord clamping is associated with increased neonatal hemoglobin levels, and improved iron status in infants at 4–6 months. There are no previous studies evaluating effects from timing of clamping on development in term infants. Objective Does the time for umbilical cord clamping affect psychomotor development evaluated with Ages and Stages Questionnaire (ASQ) in 4-month infants? Design/methods Randomized controlled trial investigating effect of delayed cord clamping (≥180 sec, DCC) versus early cord clamping (≤10 sec, ECC) in 382 full-term normal deliveries. After 4 months, parents reported their infant’s development by the ASQ. Results 365 (96%) questionnaires were returned. The mean total ASQ score did not differ between groups. The DCC group had a higher mean score (SD) in the domain problem solving, 55.3 (7.2) vs. 53.5 (8.2), p=0.03 and a lower score in personal-social; 49.5 (9.3) vs. 51.8 (8.1), p=0.01. There were no difference between the DCC and ECC groups concerning the frequency of infants under cut-off score (table). Conclusions There was no overall effect of DCC on neurodevelopment assessed at 4 months of age. The possible effects on the domains will be further investigated in a follow-up study.

Background: Iron deficiency anaemia remains a serious public health problem worldwide, especially in young children. There are many indicators of iron status, which are usually used in combination since they all have limitations. Reticulocyte haemoglobin content (RetHe) is a novel biomarker of iron deficiency but there is a lack of reference limits for RetHe in infants. Aim: To provide reference limits in healthy infants. Methods: Swedish infants (n=392) born vaginally, at term and in uncomplicated perinatal circumstances were included. RetHe was measured and correlated to Haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin concentration (MCHC), ferritin, soluble transferrin receptor (sTfR) and transferrin saturation (TS). Results: Of the infants, 46% were boys, mean (SD) birth weight was 3575 (±479) grams and mean gestational age was 40,1 (±1,1) weeks. At 12 months, 324 infants (85%) remained in the study. RetHe is presented in Table 1. At 4 months, we found significant correlations (p< 0.001) between RetHe and MCV, MCHC, ferritin, sTfR and TS, and at 12 months between RetHe and Hb, MCV, MCHC, sTfR and TS. Table Conclusion: This is the largest study presenting RetHe reference limits for infants. Defining a reference range for RetHe is a first step towards standardizing RetHe as a pre-anaemic biomarker for iron-deficiency in children.

174 Early Versus Late Cord Clamping: Neonatal Outcomes and Iron Status at 4 Months in Swedish Infants

When the major light-absorbing pigments in bacterial photosynthesis are non-covalently bound to their apo-protein (antenna apo-protein and reaction center subunits) their absorption spectra show well-defined red-shifts. The origin of these shifts has been subject of a lot of conjectures.

Carotenoids have two important functions in photosynthetic light-harvesting systems. One function is to protect the organism from harmful singlet oxygen. The second is to absorbe light in the blue part of the solar spectrum and transfer the excitation energy to chlorophyll or bacteriochlorophyll chromophores. For both biological processes an understanding of the photophysics of carotenoids is of primary importance.

(1979). A SUPPLEMENT TO FREUD'S CASE HISTORY OF “FRAU EMMY v.N.” IN STUDIES ON HYSTERIA 1895. The Scandinavian Psychoanalytic Review: Vol. 2, No. 1, pp. 5-16.

The incidence and prevalence of registered and psychiatric disorders were studied from birth to 24 years of age in a total population. The cumulative incidence of psychiatric disorders (meeting DSM III criteria) below 25 years was 13.9% for boys and 14.2% for girls. The outcomes of psychiatric disorders during childhood were generally good. Only 11% of children with an onset before age 10 remained in psychiatric care as young adults. Psychiatric disorders were more common among boys who had attended special classes. Low intelligence was related to psychiatric disorders with an onset before 15 years of age in males, but after 15 in females.

SummaryThe hemostatic effect of progesterone administered vaginally at a dose of 100 mg twice a day throughout one menstrual cycle was investigated and compared with the coagulation factors in one untreated normal menstrual cycle in 15 women. The progesterone treatment resulted in a 20-fold progesterone rise in the early follicular phase from 1.2 nmol/1 in the pretreatment control cycle to levels between 26 and 29 nmol/1 during treatment. Ovulation was completely suppressed in seven women while eight women showed a slight rise in progesterone on treatment days 20 to 25 not compatible with the rise which could have been expected if ovulation had occurred. The effects found on haemostasis during progesterone treatment varied with the menstrual cycle and were so small that they could as well be due to chance and not to treatment.

We study risk taking on behalf of others, both with and without potential losses. A large-scale incentivized experiment is conducted with subjects randomly drawn from the Danish population. On average, decision makers take the same risks for other people as for themselves when losses are excluded. In contrast, when losses are possible, decisions on behalf of others are more risky. Using structural estimation, we show that this increase in risk stems from a decrease in loss aversion when others are affected by their choices.

We study risk taking on behalf of others, both when choices involve losses and when they do not. A large-scale incentivized experiment with subjects randomly drawn from the Danish population is conducted. We find that deciding for others reduces loss aversion. When choosing between risky prospects for which losses are ruled out by design, subjects make the same choices for themselves as for others. In contrast, when losses are possible, we find that the two types of choices differ. In particular, we find that subjects who make choices for themselves take less risk than those who decide for others when losses loom. This finding is consistent with an interpretation of loss aversion as a bias in decision making driven by emotions and that these emotions are reduced when making decisions for others. This paper was accepted by Uri Gneezy, behavioral economics.

Recent experimental evidence suggests that noisy behavior correlates strongly with personal characteristics. Since decision noise leads to bias in most elicitation tasks, there is a risk of falsely interpreting noise-driven relationships as preference driven. This puts previous studies that found a negative relation between personality measures and risk aversion into perspective and in particular raises the question of how to achieve robust inference in this domain. This paper shows, by way of an economic experiment with subjects from all walks of life, that using structural estimation that models heterogeneity of noise in combination with a balanced design allows us to mitigate the bias problem. Our estimations show that cognitive ability is related to noisy behavior rather than risk preferences. We also find age and education to be strongly related to noise, but the personality characteristics obtained using the Big Five inventory are less related to noise and more robustly correlated to risk preferences.

Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Structural estimation allowing for heterogeneity of noise yields no significant relation between risk aversion and cognitive ability. Our results suggest that cognitive ability is related to random decision making, rather than to risk preferences.