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Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations.Results: In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046).Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells. Clin Cancer Res; 17(12); 4136–44. ©2011 AACR.

Supplementary Materials and Methods from T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab

To identify common resilience factors against non-communicable diseases (dental caries, diabetes type II, obesity and cardiovascular disease) among healthy individuals exposed to chronic adversity.The databases MEDLINE (via PubMed), Scopus and CINAHL were searched. Observational studies in English assessing resilience factors among populations living in chronic adversity were included. Intervention studies, systematic reviews, non-original articles and qualitative studies were excluded. There were no restrictions regarding publication year or age. No meta-analysis could be done. Quality assessments were made with the Newcastle-Ottawa scale (NOS).A final total of 41 studies were included in this systematic review. The investigated health resilience factors were divided into the following domains: environmental (community and family) and individual (behavioural and psychosocial). A narrative synthesis of the results was made according to the domains.Individual psychosocial, family and environmental factors play a role as health resilience factors in populations living in chronic adversity. However, the inconclusive results suggest that these factors do not act in isolation but interplay in a complex manner and that their interaction may vary during the life course, in different contexts, and over time.

In the randomized, placebo-controlled, double-blind trial ‘Palliative-D’, vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; −1.50 ESAS points (95%CI −2.57 to −0.43; p = 0.007) but not in women; −0.75 (95%CI −1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (−0.33 (95%CI −0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.

In the randomized, placebo-controlled, double-blind trial ‘Palliative-D’, vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; −1.50 ESAS points (95%CI −2.57 to −0.43; p = 0.007) but not in women; −0.75 (95%CI −1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (−0.33 (95%CI −0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.

Background: Fatigue is one of the most distressing symptoms in patients with advanced cancer. Previous studies have shown an association between low vitamin D levels and fatigue. Objectives: The ai...

Earlier animal studies have provided evidence that non-Hodgkin lymphoma (NHL) may be caused by exposure to radiofrequency (RF) radiation. This was recently confirmed by the U.S. National Toxicology (NTP) study that showed an increased incidence of malignant lymphoma in female mice exposed to the GSM modulated or the CDMA modulated cell phone RF radiation. Primary central nervous system lymphoma (PCNSL) is a rare malignancy in humans with poor prognosis. An increasing incidence has been reported in recent years. Based on a case-report we present the hypothesis that use of the hand-held mobile phone may be a risk factor for PCNSL. The increasing incidence of non-Hodgkin lymphoma in Sweden is discussed in relation to etiologic factors.

Objective: At the initiative of Stockholm County Council, a survey was performed by an independent investigator to evaluate satisfaction among patients and their families with the advanced palliative home care teams in the county of Stockholm. The survey was performed in 2010 and compiled in 2011. The aim was to evaluate the impressions of patients and their families of the support given by the palliative home care teams in the Stockholm area and to evaluate the management of symptom control, availability, continuity, confidence, and quality of communication. Methods: A questionnaire was sent to 1424 patients and 329 family members to evaluate the views of the users of the home care service. Results: The response rate was 78% among both patients and their families or other caregivers. The proportion of positive and very positive responses among those who needed the specific help of the team was as follows: information about the service 86%, availability around the clock 96%, influence and feeling of shared responsibility 88%, and possibility of family members to have supportive discussions 95%. Eighty-three percent of patients experienced total pain relief and 99% total or partial relief. The corresponding figures for anxiety were 77% and 97% and for other symptom reliefs 79% and 98%, respectively. These figures were comparable to a smaller survey in 2014 and were high compared to the results from other medical services using similar questionnaires. Significance of the Results: A high quality of care is possible to achieve within palliative home care services.

According to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life (QoL) without having any significant side effects.The primary objective of the 'Palliative-D' study is to test the hypothesis that vitamin D supplementation for 12 weeks reduces opioid consumption. The secondary objectives are to study if reduction of antibiotic consumption and fatigue as well as improvement in QoL assessments can be observed. Effect on the 25-hydroxy vitamin D (25-OHD) levels in serum after 12 weeks of treatment will be studied, as well as the change in opioid dose in relation to genetic polymorphism in genes involved in the effect and metabolism of vitamin D.A randomised, double-blind placebo-controlled multicentre trial has been designed. The trial will include 254 adult palliative cancer patients with 25-OHD levels50 nmol/L and a life expectancy of more than 3 months recruited from two advanced palliative home care centres in Stockholm. Included patients will be randomly assigned to 12 weeks of treatment with cholecalciferol (vitamin D3) 4000 IU/day or placebo. The study will start in November 2017 and will finish in December 2019. The study is approved by the Regional Ethical Committee, Dnr2017/405-31/1, by the Swedish Medical Products Agency, EudraCT: 2017-000268-14, and is registered at Clinicaltrial.gov: NCT03038516. The study is financed with research grants from the Swedish Cancer Society and the Stockholm County Council.

Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early - based on the median observation time of 4 years - results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6·5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7·4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL. The study was registered at www.isrctn.org as ISRCTN 87866680.

Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations. Results: In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046). Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells. Clin Cancer Res; 17(12); 4136–44. ©2011 AACR.

Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPIB (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPIB is feasible. This trial was registered at www.isrctn.org as #ISRCTN 87866680.

Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m2 weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.

The University Hospital in Akureyri (Centre for Emergency Medical Service (EMS) Education) in Iceland, Emergency & Disaster Medical Centre (AKMC) in Sweden and National Health Service - Western Isles in Scotland have undertaken a project “Ambulance Transport and Services in the Rural Areas” (ATSRuAr); the object of this paper is to provide an overview of the present status of ambulance transport and services in the three participating regions. This is a project of the INTERREG III Northern Periphery Programme (NPP) who provided a grant for the work. Methods Each partner reviewed the current status of prehospital services in their country or region and presented the results at a project meeting in Iceland in March 2006. Results and Conclusion Geography and weather provide a challenge to the ambulance transport and services in sparsely populated northern rural areas. The Emergency Medical Services (EMS) systems in these three northern rural areas have many similarities. However, there are differences in the number and distribution of ambulances, the running of the service, education and training of ambulance personnel and first responder schemes. This collaboration will debate on the provision of ambulance transport. Research is needed to indicate how improvements in ambulance transport can improve patient outcome in rural areas.

The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18–75 years were eligible. Thirty-nine patients aged 18–65 years and 27 patients aged 66–75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%–47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%–61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64–75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730) © 2015 Ferrata Storti Foundation.This is an open-access paper.

Background: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. Patients and methods: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. Results: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. Conclusions: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov.identifier: NCT01502982.

Background Persistent organic pollutants (POPs) are lipophilic chemicals that bioaccumulate. Most of them were resticted or banned in the 1970s and 1980s to protect human health and the environment. The main source for humans is dietary intake of dairy products, meat and fish. Little data exist on changes of the concentration of POPs in the Swedish population over time. Objective To study if the concentrations of polychlorinated biphenyls (PCBs), DDE, hexachlorobenzene (HCB) and chlordanes have changed in the Swedish population during 1993–2007, and certain factors that may influence the concentrations. Methods During 1993–2007 samples from 537 controls in different human cancer studies were collected and analysed. Background information such as body mass index, breast-feeding and parity was assessed by questionaires. Wilcoxon rank-sum test was used to analyse the explanatory factors specimen (blood or adipose tissue), gender, BMI, total breast-feeding and parity in relation to POPs. Time trends for POPs were analysed using linear regression analysis, adjusted for specimen, gender, BMI and age. Results The concentration decreased for all POPs during 1993−2007. The annual change was statistically significant for the sum of PCBs −7.2%, HCB −8.8%, DDE −13.5% and the sum of chlordanes −10.3%. BMI and age were determinants of the concentrations. Cumulative breast-feeding > 8 months gave statistically significantly lower concentrations for the sum of PCBs, DDE and the sum of chlordanes. Parity with > 2 children yielded statistically significantly lower sum of PCBs. Conclusions All the studied POPs decreased during the time period, probably due to restrictions of their use.

Prenatal diagnosis was performed in 81 cases at risk for the fragile X syndrome. There were 12 fra (X)-positive cases, two of which showed low expression in cultured amniotic fluid cells. FUdR and high thymidine were used for induction of fra(X) (q27.3) expression in all cases. In 21 cases linkage studies were performed, 7 with probes for the loci DXS52, DXS98 and DXS105, 13 with probes for DXS369 and DXS296, DXS304 or DXS374 and one with the probe Do33 for DXS465. In 11 of these cases linkage analysis gave risk figures higher than 95% or lower than 5%, all in concordance with the cytogenetic findings. Discordance was found in three cases studied earlier, the two cases with low expression mentioned above and one cytogenetically normal case, which were now restudied with the new probes. RFLP-studies and linkage analysis was also performed for 24 cytogenetically fra(X)-negative females having a 50%, 25% or 12.5% risk of being carriers according to pedigree data. In 15 cases the risk dropped to 1% or less. Six of these women were pregnant and had asked for prenatal diagnosis but after genetic counseling prenatal diagnosis was avoided.

Many students feel insecure making their first attempts to solve programming problems. Despite finishing the introductory programming course successfully, these students refrain from pursuing their CS studies. Hence, this aversion towards problem solving and programming is not fully explained by lack of subject understanding and performance. In order to better understand the components of students' comfort, a first attempt to model a student's confidence regarding problem solving and programming has been made. The model consists of two dimensions; Course topic and Student's mindset. Two questionnaires have been developed in order to capture if and how students' confidence is affected by taking the CS1 course. Data has been collected for four course offerings with three different study programmes. Results confirm the suspicion that the confidence is lowered by the course, and that student groups with different ambition and motivation for taking the course seem to be affected by different aspects of the course.

For unknown reasons the incidence of non-Hodgkin's Lymphomas (NHL) has increased during the last decades. Conditions with impaired immune functions have been associated with an increased risk of malignant lymphomas. Interactions between the central nervous, immune, and endocrine systems have been recently identified, and the potential physiological importance of these interactions is being explored. In this prospective cohort study the potential association between an increasing incidence of depressive disorders and the development of malignant lymphoma is being explored. The participants were part of the Swedish manpower on sick leave between 1988 and 2000 with depressive disease for more than two weeks were followed until a diagnosis of lymphoid malignancy, death, emigration, or end of follow-up period. The final cohort included 87,677 individuals with 373,135 years of follow-up. There were 80 cases of NHL, chronic lymphocytic leukemia (CLL), and Hodgkin lymphoma (HL) with 70 cases expected. The first year of follow-up showed a slightly increased risk of NHL, which most probably can be interpreted as initial symptoms of lymphoma. We conclude that the increase in the incidence of malignant lymphomas observed during the last decades seems not to be associated with a concurrent increase of depressive disorders.

In recent years, students have become less active, resulting in lower attendance in lectures and practical sessions. In addition to this, the number of students enlisting in our programmes has decreased. Moreover the passing rates for initial courses have dropped severely. This generates problems because the students failing first year courses cannot move on to higher level courses. Not only can this be devastating for individual students, but it can also affect the variety of higher level courses. In an attempt to prevent these problems we focused on the introductory programming courses (CS1) in order to enhance the opportunities for the students to become successful. One action taken was a research project initiated to radically change the way object-oriented programming is taught in CS1. Another action was to introduce the supplemental instruction programme (SI). SI helps students master content while they develop and integrate learning and study strategies. This paper will give a short introduction to these actions. Results are presented along with a discussion concerning the problems in teaching object-oriented concepts and problem solving.

The aim of this study was to evaluate the association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkin's lymphoma (HL). A Swedish cohort of 27,150 HCV-infected persons notified during 1990-2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person-years, and to identify all incident malignancies in the cohort. The patients were stratified according to assumed time of previous HCV infection. The relative risk of malignancy was expressed as a standardized incidence ratio (SIR)-the observed number compared to the expected number. During 1990-2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person-years. The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection (SIR 1.89 [95% CI, 1.10-3.03] and 2.54 [95% CI, 1.11-5.69], respectively). The association was not significant in TC or CLL. In conclusion, we report the incidence of several malignancies in a nationwide cohort of HCV-infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of NHL and MM.

The transition to object-oriented programming is more than just a matter of programming language. Traditional syllabi fail to teach students the "big picture" and students have difficulties taking advantage of object-oriented concepts. In this paper we present a holistic approach to a CSI course in Java favouring general object-oriented concepts over the syntactical details of the language. We present goals for designing such a course and a case study showing interesting results.

Increased risk for non-Hodgkin's lymphoma (NHL) following exposure to certain pesticides has previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI 95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.

In 1971 Dijkstra noted that as a teacher of programming he 'feels akin to a teacher of composition at a conservatory. He does not teach his pupils how to compose a particular symphony, he must help his pupils to find their own style and must explain to them what is implied by this' [1]. In similar vein, Don Knuth suggests that 'computer programming is an art, because it applies accumulated knowledge to the world, because it requires skill and ingenuity, and especially because it produces objects of beauty' [2].Traditionally, most Computer Science programs offer an introductory programming methodology course (CS1). In recent years, many institutions have subjected this course to major changes. One common alteration has been a move from a procedural paradigm to an Object Oriented (OO) paradigm. In many cases, this is manifested as a change to programming in Java. Emerging from this transition is the apparent anomaly that many students fail to understand OOP concepts, especially when required to use them in problem solving.Our panel represents researchers from four different countries who have all encountered such problems with a CS1 course. In this light, the panel focuses on CS1 difficulties and aims to address solutions to the 'Java problem'. Although we bring our own insights to the considered issues, we aim to engage the panel audience in discussing the nature of the problem and the propriety of the proposed solutions.

Abstract 747 The outcome of mantle cell lympoma (MCL) has improved in recent years. The Nordic Lymphoma Group has since 1996 completed three consecutive phase II trials for front-line treatment of MCL patients < 66 years of age. The first trial (MCL1) showed that quality of response prior to transplant was the most important factor for outcome. Hence, in the second trial (MCL2) induction therapy was intensified by adding cycles of high-dose Ara-C and rituximab to the regimen. Despite significant improvement in overall and progression-free survival, patients who did not achieve CR pretransplant had a shorter time to progression. Therefore, the main objective of the MCL3 study was to improve the time to progression in patients who achieved only CRu or PR pretransplant by adding Zevalin to the high-dose regimen as a late intensification. Results of the – otherwise largely identical - MCL2 trial serve as the historic control. Methods: Newly diagnosed stage II-IV MCL patients < 66 years received induction immunochemotherapy with alternating cycles of R- (rituximab) maxi-CHOP and R-Ara-C to a total of 6 cycles. Evaluation of pretransplant response with CT scans and bone marrow was performed after 5 cycles. PET/CT pretransplant was recommended, but would not influence treatment. Responding patients by NCI criteria underwent in-vivo purged stem cell harvest after the 6th cycle (Ara-C + 2 doses of rituximab). Patients in CRu or PR received a standard dose Zevalin (0.4 mCi/kg) one week prior to high-dose therapy with BEAM or BEAC while CR patients received the high-dose chemotherapy without Zevalin. Follow-up included CT-scans, bone marrow and blood sampling for at least 5 years, including PCR for minimal residual disease or molecular relapse. Patients in solely molecular relapse received preemptive therapy with 4 weekly doses of rituximab, as in the MCL2 study. Results: 161 consecutive patients were included from 2005–2009, with characteristics similar to that of the MCL2 trial with a median age of 57 years (28–65), a male predominance and the majority in stage IV with bone marrow involvement. Only 12 out of 161 patients (7 %) did not receive a transplant, 6 due to stem cell harvest failure, 2 due to toxicity and 4 due to no response to induction treatment. Before transplant 50% were in CR, 17% in CRu, and 30% in PR. Only four out of 161 patients (2 %) did not respond to induction treatment. After a median follow-up of 3.2 years the projected 5-year overall and event free survival, and time to progression were 71, 55 and 65% respectively and the MCL2 and MCL3 curves were superimposable. Of the 69 candidates to Zevalin in CRu/PR according to protocol, 65 (94%) actually received this treatment. There was no significant difference in time to progression for patients in CRu and PR pretransplant between MCL2 and MCL3, indicating no effect of late intensification with Zevalin in MCL3 in this patient group. Interestingly, a positive pretransplant PET scan proved to be a strong negative predictor for outcome. Lack of benefit from addition of Zevalin to the high-dose regimen was shown for both PET-positive and PET-negative patients. In a multivariate analysis of the impact of clinical response, PET positivity and zevalin treatment, only PET positivity pretransplant had independent significance (p=0.0003 HR=3.412 (95% confidence limits 1.744 – 6.673). The treatment-related mortality was 3 %. Side-effects were similar to that previously reported for MCL2, and we did not find that Zevalin added any toxicity. Of the 3 patients who developed secondary MDS/AML posttransplant, two had received Zevalin and one had not. Conclusion: The MCL3 data confirm the good results and tolerability of the Nordic regimen. However, the late intensification with Zevalin, albeit non-toxic, did not prolong the time to progression for patients in only CRu or PR pretransplant. A positive PET prior to transplant was shown to be a strong negative predictor for outcome. The concept of late intensification may be too late in poor responders. In consequence, up-front intensification with increasing use of high-dose AraC for MIPI high-risk patients is used in the subsequent, now ongoing Nordic-British MCL5 study. Disclosures: Arne: Bayer Schering Pharma: Research Funding. Geisler:Roche, Schering: Consultancy, Research Funding.

Abstract 794 Introduction/Purpose: The optimal treatment schedule and best order of therapies are not well established for patients (pts) with indolent lymphoma. The aim of this trial was to evaluate the effect of adding interferon-alpha (IFN) to first-line rituximab (R) monotherapy, with extended dosing, in pts with CD20+indolent lymphoma and to define pts with no need of initial chemotherapy. Patients and methods: Pts with symptomatic, advanced indolent lymphoma (previously untreated or at first relapse after a short course of chlorambucil) were randomized to R (MabtheraR) 375 mg/m2 once-weekly for 4 consecutive weeks or R with 5 weeks IFN (Roferon-AR) as priming. Patients achieving either a complete response (CR), partial response (PR) or a minor response (MR) at evaluation 6 weeks after last R in this first cycle, were planned to receive a second cycle with four infusions of R alone or combined with IFN, according to the initial randomization. Primary endpoint was time to treatment failure (TTF), defined as the time period from randomization to one of the following events: progressive disease during treatment, death of any cause or initiation of new therapy. Results: In total, 313 patients were randomized. The median age was 59 years, 51% were females, 90% Ann Arbor stage III or IV and 31% showed elevated LDH. The clinical characteristics were well-balanced between the treatment groups. Pathology review showed 127 follicular lymphoma (FL) grade I, 110 grade II and 9 grade IIIA. In total, 4 pts in each arm did not fulfill inclusion criteria: 5 DLBCL/ transformed, 2 MCL and one Hodgkin. Most patients were previously untreated, but 10 pts in the R group and 13 with R+IFN had had a previous response to chlorambucil and 18 and 9 had had local radiotherapy. respectively. After cycle 1, response rates among all 313 randomized pts were 8.6 % CR/CRu, 47.9 % PR, 22.4 % MR and 16.9 % of pts were considered resistant (SD/PD). In total 244 pts were qualified for cycle 2. Overall response rates after cycle 2 were 82% and 74%, in the R+IFN- and the R-group, respectively (n.s), but the CR/CRu rates were higher with the combination (41% vs 22.4%, p< 0.01). Also pts with FLIPI 3–5 (45% of all pts) showed a deeper response with R+IFN (CR/Cru 38.0% compared to 23.1%). More patients in the combination arm improved their responses from PR/MR in cycle 1, to CR after cycle 2. In the intention–to treat (ITT) population (n=313), median time to TTF was 21 and 28 months in the R and R+IFN group, respectively. Most events consisted of initiation of new therapy including chlorambucil, COP or CHOP, but in 7 patients in the R group, relapse treatment was single R (in one case with the addition of IFN) and in the R+IFN group 10 pts had R (3 with IFN). Two pts in the R-group and 12 pts in the R+IFN group had late relapses treated with local irradiation. After a median follow-up time of 60.7 months, for surviving pts, 35 % of the ITT patients were still event-free with 90% survivors, but with no difference between the treatment groups. Patients with FL grade II and IIIA showed a longer TTF than pts with grade I (p=0,05). Conclusion: This randomized phase III trial demonstrates that extended rituximab therapy is safe and effective as first-line therapy in patients with symptomatic low-grade B-cell lymphoma, with improved responses and a delayed time to early failure if combined with IFN. The long term FU suggests that more than 1/3 of this patient population does not need initial chemotherapy, but predictive markers for response to R and new biological combinations are needed. Disclosures: Kimby: Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees.

Abstract 1602 Patients and Methods: From May 2007 to October 2010, 66 newly diagnosed primary central nervous system lymphoma (PCNSL) patients (M/F ratio 1: 1) were enrolled. Younger patients (≤65 yrs; N=39) received 6 three-weekly cycles of chemotherapy consisting of: high-dose (HD)-methotrexate (MTX) (cycles 1, 2, 4 and 5), HD-cytosine arabinoside (AraC) (cycles 3 and 6) in addition to Rituximab (cycle 1 only), ifosfamide (cycles 1 and 4), cyclophosphamide (cycles 2 and 5), vincristine (cycles 2 and 5), vindesine (cycles 3 and 6), and dexamethasone (all 6 cycles). Depocyte® was delivered intratechally during the HD-MTX cycles. Elderly patients (66–75 yrs; N=27) received an identical Rituximab-containing 1st cycle. Cyclophosphamide and ifosfamide were replaced by temozolamide (cycles 2 to 6), which was also given as maintenance in patients with chemosensitive disease, and vincristine was omitted. No radiotherapy was given. Response was determined after the 2nd, 4th and 6th chemotherapy cycle by cerebral MRI and assessed according to International Primary CNS Lymphoma Coordinating Group criteria. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), overall response rate (ORR), systemic toxicity and neurotoxicity assessed as Mini Mental State Examination (MMSE) and Functional Independence Measure (FIM). Results: The median age was 64 yrs overall, 55 yrs (range 40–65) for younger and 70 yrs (range 66–75 years) for elderly patients. In 56 patients, the International Extranodal Lymphoma Study Group prognostic score was: 0–1 (N=5), 2–3 (N=36) and 4–5 (N=15). In the remaining 10 patients, lumbar puncture was not performed in five and spinal fluid protein concentration not reported in additional five cases. Response assessment after completion of induction treatment was performed in 43 out of 66 patients and showed complete remission (CR/CRu) in 30 patients, partial remission (PR) in 5 and progressive disease (PD) in 8. The ORR was 53 %. In 23 patients, response could not be evaluated due to early progression (n=8), toxic death (n=4), poor performance (n=3), neurotoxicity (n=5), or other causes (n=3). Of the 27 elderly patients, 15 continued to maintenance therapy. Of these, 14 have completed the maintenance schedule. Remission status at month 3 was CR in 13 and PD in 1 patient. With a median follow-up of 11.1 months (range 0.6–40.2) the 3-yr OS was 54.6% with no significant difference between younger and elderly patients (56.4% vs 51.9% respectively, p=0.32). The 3-yr PFS was 35.1% (32.9% in younger and 38.2 % in elderly patients; p=0.96). There were four septic deaths. Grade 3–4 hematological toxicity was seen in 79 % of the patients. Arachnoditis-like symptoms occurred in 13 patients. In all but two patients, the symptoms resolved within less than a week. MMSE and FIM were recorded both before and after therapy in 32 patients. Scores improved in 18 and 20 patients, respectively. Conclusion: In conclusion, the schedule applied in the present study led to a 3 yr PFS of 35%. Surprisingly, no significant outcome difference was found between the younger and the elderly patients. The majority of treatment failures were due to early progressive disease under induction therapy. Although the follow-up of our study is short, de-escalation of induction treatment intensity by introduction of a less toxic agent as temozolomide, and its subsequent use in a maintenance schedule may explain a possible survival benefit of this strategy in elderly patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 2805 CHOP – based chemotherapy for aggressive lymphomas in patients with age-adjusted International Prognostic Index (IPI) score of 2–3 resulted in a historical 3-year progression free survival of approximately 30% in a previous Nordic phase III study. The aim of the present study is to determine whether an intensified regimen with chemoimmunotherapy and CNS prophylaxis improves outcome. Methods: From October 2004 to June 2008 patients were included in a phase II study. Inclusion criteria: 1) Age 18–65 years. 2) Newly diagnosed de novo diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade III. 3) No clinical sign of CNS disease and negative CSF cytology/flow cytometry by lumbar puncture. 4) No HIV infection. 5) WHO performance score 0–3. 6) Adequate organ functions. Schedule: Six courses of R-CHOEP14. Pegfilgrastim 6 mg sc. day four of each cycle. One course of high dose cytarabine 12 g/m2 (6 g/m2 for patients 60–65 years). One course of high dose methtrexate 3 g/m2 (1 g/m2 for patients 60–65 years). Biopsy and/or 18FDG PET/CT imaging of residual masses after fulfilled therapy was recommended, but not mandatory. Radiotherapy was given to residual masses of uncertain significance. Results. Demographic data:.156 eligible patients were included (97 males). Median age: 54 years (range 20–64). Histology: DLBCL: 145, FL grade 3: 12 (three patients no data). Age adjusted IPI score: 2: 117; 3: 39. Stage III-IV: 150 patients. LDH elevated: 151 patients. Performance status 2–3: 51 patients. B-symptoms were registered in 97 patients, more than one extranodal site in 42 and bulky lesions (≥ 10 cm) in 68. Median observation time for patients alive at last follow up was 36 months. Toxicity: Three toxic deaths are registered, one large bowel perforation, one fulminant hepatic necrosis and one septic shock. Hematological toxicity grade 4 was seen in 78% of the patients, infection grade 4 in 8%. Radiotherapy was given to 16% of the patients. Response: Response rates at end of therapy: CR/CRu: 69%, PR: 22%, SD: 1%, PD: 4.5%. Seventeen patients (7%) were not treated according to protocol, either due to lack of response (6 patients) or due to toxicity (eleven patients). The majority of the PR patients were considered to have residual masses and not viable tumour tissue. Survival: Three year overall survival was 80% (95% CI +/− 6.5%) and three year treatment failure free time 67% (95% CI +/−8.0%). CNS events: Seven patients had a CNS relapse, all but one were isolated (4 intracerebral, 3 meningeal). All CNS relapses occurred within 6 months after inclusion. Conclusions: The results are promising with a low three year treatment failure rate, a low toxic death rate and fewer CNS events than expected. The CNS events might be further reduced by earlier CNS prophylaxis. The study was supported by an unrestricted grant from Amgen Disclosures: Holte: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. LeppÃ: Roche: Honoraria. Bjorkholm:Roche: Research Funding. Jyrkkiö:Roche: Honoraria. Kolstad:Roche: Honoraria; Amgen: Honoraria. Fosså:Roche: Honoraria. φstenstad:Roche: Honoraria; Amgen: Honoraria. Eriksson:Amgen: Research Funding.

Abstract 932 The Nordic Lymphoma Group has since 1996 conducted three consecutive phase II trials for front-line treatment of MCL patients ≤ 65 years of age. The first protocol (MCL1) 1996-2000 introduced high-dose chemotherapy with autologous stem cell support (unpurged or ex vivo purged) as consolidation after 4 cycles of intensified CHOP (maxi-CHOP). The results were disappointing, as the majority of patients relapsed. 1 Being in CR pre-transplant was the most important factor for outcome. Hence, in the second trial (MCL2) 2000-2006 induction therapy was intensified by adding high-dose Ara-C and rituximab to the regimen. Compared to MCL1 this led to significant improvement of event-free and overall survival, and the rate of PCR negative stem cell grafts and bone marrow samples.2 Again, responders in less than CR pre-transplant had a significantly poorer outcome. We therefore made a further intensification for the MCL3 study (2006-2009) by adding 90Y-Ibritumomab tiuxetan (Zevalin®) to the high-dose BEAC/BEAM to responders not in CR. Methods: As in the MCL1 and 2 studies newly diagnosed stage II-IV MCL patients ≤ 65 years were included. Induction treatment was identical to that of the MCL2 study with alternating cycles of maxi-CHOP-rituximab (3 cycles) and Ara-C-rituximab (3 cycles). Response evaluation was done after cycle 5. PET/CT was recommended, but could not influence the response evaluation, which was done according to the International Workshop criteria. Responders underwent in vivo purged harvest of stem cells after cycle 6 (Ara-C + 2 doses of rituximab). Patients in CRu or PR received a standard dose 90Y-Ibritumomab tiuxetan (0.4 mCi/kg) one week prior to the BEAM/BEAC, CR patients received BEAM/BEAC alone. Patients are followed by CT-scans, bone marrow and blood samples, including PCR for minimal residual disease or molecular relapse. For molecular relapse preemptive treatment with 4 standard doses of rituximab, as in the MCL2 study3, is given. Results: The planned accrual of 160 patients was reached in June 2009. The patient characteristics are similar to those of the MCL2 trial with a median age of 57 years (28-65), the majority male (80%) and in stage IV (89%) with bone marrow involvement (74%). The response rates pre-transplant so far compare favorably with data from MCL2 with 50% in CR, 18% in CRu, and 28% in PR. Only 4 out of 128 evaluable patients did not respond (3%) and there was one case (1%) of treatment-related mortality during induction therapy. While it is still too early to assess the impact of the 90Y-Ibritumomab tiuxetan on the progression-free survival, the side effects were similar to those of the MCL2 study including a treatment related mortality of 4%. Fifty-five patients in CRu or PR have so far been treated with 90Y-Ibritumomab tiuxetan, with no indication of any added toxicity. Only 12 out of 133 patients (10%) have not undergone transplant, 5 due to stem cell harvest failure, 3 due to toxicity and 4 due to non response to induction treatment. PET-scan prior to transplant was positive in 2% of CR patients, 20% of CRu patients and 54% of PR patients. Patients with a positive PET-scan pre-transplant had a 36% chance of achieving a molecular remission post-transplant, compared to 92% of cases with a negative PET-scan (p Conclusion: The high response rates after induction treatment achieved in the MCL2 study are confirmed in the present study. Adding 90Y-Ibritumomab tiuxetan to high-dose chemotherapy for responding patients not in CR prior to transplant is feasible and does not increase toxicity. A negative PET-scan prior to transplant predicts for a molecular remission after the transplant. References: Andersen et al, Eur J Cancer, 2002, 38: 401-408 Geisler et al, Blood, 2008, 112: 2687-2693 Andersen et al J Clin Oncol 2009 epub ahead of press Disclosures: Kolstad: Bayer Schering Pharma: Research Funding. Geisler:Bayer Schering Pharma: Research Funding.

Mantle cell lymphoma (MCL) is considered incurable, with a median survival of 4 years. Intensive immunochemotherapy and autologous stem-cell (ASC) support has appeared promising in small patient cohorts, but has not been tested in large, consecutive series. Here we report the final results of the 2nd Nordic MCL (MCL2) trial after a median of 3 years follow-up from study entry. Methods: This unrandomized phase-II trial included 159 untreated patients younger than 66 years, 84% stage IV, 128 with classical, 31 with blastoid/pleomorphic cytology. Following 6 cycles of intensive induction immunochemotherapy with alternating cycles of rituximab (R) + maxi-CHOP and R+ high-dose AraC, responders received BEAM/BEAC with in-vivo purged (R) ASC support. Results: 153 patients (96%) responded to induction therapy with CR in 55% and PR in 41%. The 5-year event-free (EFS) and overall survival (OAS) are 63% and 74% respectively on intention-to-treat, and the 144 (91%) responders who completed treatment had 72% 5-year response duration, with plateaus emerging in all three curves at these levels. Figure Figure There were 6 treatment-related deaths (3,8%). Of 77 patients with available primers, 90% had become PCR-negative two months posttransplant; those who remained PCR-negative more than 1 year posttransplant had a significantly longer clinical response duration than patients who did not (P Conclusion: The demonstration of long-term event-free survival in a large, consecutive prospective series now for the first time indicates that intensive immunochemotherapy including AraC and Rituximab with in-vivo purged stem-cell support may cure mantle cell lymphoma.

The 2nd. Nordic Lymphoma Group mantle cell lymphoma (MCL2) protocol has demonstrated the importance of Ara-C and Rituximab in the induction chemotherapy and stem-cell mobilisation before high-dose therapy and autologous stem-cell transplant (1). By July 2005, 128 patients (83% stage IV) had completed protocol treatment consisting of 3 series of R-CHOP and 3 series of R-Ara-C, stem-cell harvest and high-dose therapy with BEAM/BEAC with ASCT. The 5-year failure-free and overall survival is 50% and 83% respectively, significantly higher than the historic control group of the Nordic MCL1 protocol with the same treatment without HD-Ara-C and Rituximab (P Of 75 patients with molecular markers who had completed treatment, 55 remain PCR-negative and 20 have become/remained PCR-pos. posttransplant. Clinical relapse ocurred significantly more often in the latter group (11 of 20) than in the PCR-neg. patients (4 of 55) (P Ten of the 20 PCR-positive patient did not receive preemptive rituximab: five due to immediate clinical relapse, 2 due to stable qPCR signals, one due to protocol error and two await treatment. Of 10 patients who did receive preemptive rituximab 8 again became PCR-negative and 2 remain PCR-positive. Six of the 10 Rituximab treated patients remain in clinical and molecular remission 200–600 days after the Rituximab treatment (Fig. 2). Conclusions: In MCL, molecular relapse is a harbinger of imminent clinical relapse, whereas continuous molecular remission is associated with prolonged disease-free survival (89% at 4 years) Rituximab preemptive treatment can reinduce molecular remission and may delay clinical relapse. Following molecular relapse, only Rituximab treated patients (6 of 8 evaluable) remain disease-free. FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE. FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE.

The copy numbers of the FII plasmids R1 and R100 were determined in four different ways and found to be identical. Deletion of one of the copy number control genes, copB, together with its promoter gives rise to plasmid copy mutants with an increased copy number. The increase was found to be 8- and 3.5-fold for plasmids R1 and R100, respectively. These deletion derivatives were found to be extremely sensitive to the presence of CopB activity from their own parent plasmid but not to that of the other plasmid. Hence, the CopB protein and its target are plasmid-specific and not FII-group-specific. These results are consistent with the high degree of nonhomology between plasmids R1 and R100 in a 250-bp region covering the distal part of the copB gene and the repA promoter region, which contains the target for the CopB protein.

Site-specific deletions and insertions in the replication region of plasmid R1 have generated a new class of copy mutants that are present in the cell with 10-15-fold increased copy number. All mutations described inactivate a copy number control gene which is distinct from another cop inc gene that was identified previously (Molin and Nordström 1980). Insertion of the lac operon lacking the normal lac promoter has been used to determine the direction of transcription of this cop gene. The mutants may all be complemented by wild-type plasmid derivatives and are thus recessive. In incompatibility tests with wild-type R1 plasmids, these mutants are indistinguishable from the wild-type plasmid. It therefore seems that this cop function does not play an important role for the incompatibility function. A polypeptide, molecular weight 11,000, has been identified as being the product of this cop gene.

An attempt to find new ways to popularize science and encourage more women into it by demonstrating the scientific content of women's traditional work is described. The idea was to teach scientists textile knowledge and to teach those interested in textiles, science. Scientists could be given a course in textile dyeing and the textile group could illustrate a scientific problem in textiles. The plans to give a course in textile dyeing had to be postponed but the textile illustration of a scientific problem went well. Seventy students illustrated their thoughts on gene technology in six different works. Four of these were exhibited at an official commercial exhibition. One entitled ‘The Pyramid’ aroused especially strong feelings. The textile works showed that the new knowledge could be achieved through textiles.

A fungus, Aspergillus fumigatus Fres., which used bark as its sole carbon and energy source, was isolated. Difficulties arose in measuring fungal growth, since the hyphae and the bark could not be separated. Measurement of the weight loss of the solid material did not quantitatively estimate fungal growth. Therefore, two methods were developed to estimate fungal mass when the carbon and energy source is particulate and contributes to the parameter used as a measure of growth. They were based on determination of nitrogen either in the solid material or in the medium. The nitrogen concentration in A. fumigatus was found to be nearly constant throughout the growth cycle and to be independent of the carbon and nitrogen concentrations in the medium but to vary with the carbon source used.Aspergillus fumigatus was grown at 37C as a submerged culture in salts medium with finely ground bark from Picea abies as sole carbon and energy source. The bark medium was heat-sterilized before inoculation with spores. The fungus utilized cellulose and hemicellulose but not lignin. Substances solubilized from the bark contributed to the growth. The yield was the same on unextracted as on water-extracted bark, although growth was delayed on the former. Growth was rapid and comparable to growth on other polymeric polysaccharides, i.e. starch. Aspergillus fumigatus degraded 32–40% of the polymeric part of the bark within 4 days and with an economic coefficient of about 50%.