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Even when a screening study has demonstrated a mortality reduction, the degree of pre-testing and contamination is of importance as it can dilute the "true" effect of screening. Our object was to describe the level of pre-testing and contamination in the Göteborg-1 prostate cancer screening trial.A total of 20,000 men, 50-64 years old, were invited in 1994 and randomized to either a screening group (offered prostate specific antigen testing every 2 years) or to a control group. Follow-up was through December 31, 2014. Outcome measurement was overall testing in the screening group and control group. A positive prostate specific antigen test was defined as a prostate specific antigen ≥3 ng/ml.In the study, 4.2% in the screening group and 4.6% men in the control group were tested before study start. During follow-up, 72% in the control group took at least 1 prostate specific antigen test (contamination) compared to 87% of men in the screening group. Of all prostate specific antigens, 24% in the screening group and 39% in the control group were above threshold. In total, 66% of the men underwent prostate biopsy within 12 months from a raised prostate specific antigen in the screening group and 28% in the control group.Similar proportions of men were prostate specific antigen-tested in both the screening group and control group, yet only a minority of contamination prostate specific antigens led to biopsy. Also, men in the screening group started screening at a younger age. These could both be explanations for our result that organized screening is more effective in reducing prostate cancer mortality than non-organized testing. When carried out properly and compared to an unscreened population, the effects of organized screening are likely even greater than previously shown in the Göteborg screening trial.

Background Postpancreatectomy hemorrhage grade C (PPH C) is a dreaded complication after pancreaticoduodenectomy (PD) with high mortality rate. Concurrent risk factors for PPH C have been difficult to recognize. Connection between postoperative pancreatic fistulas (POPF) and PPH C is well known, but POPF is often unknown prior to the PPH. The aim of this retrospective study was to define potential predictive factors for PPH C. Methods Retrospectively, 517 patients who underwent PD between 2003 and 2018 were included in the study. Twenty-three patients with PPH C were identified, and a matched control group of 92 patients was randomly selected. Preoperative data (body mass index, cardiovascular disease, history of abdominal surgery, biliary stent, C-reactive protein (CRP), ASA-score), perioperative data (bleeding, pancreatic anastomosis, operation time), and postoperative data (CRP, drain amylase, POPF, biliary fistula) were analyzed as potential predictors of PPH C. Results High postoperative CRP (median 140 mg/L on day 5 or 6) correlated with the development of PPH C (p Discussion High postoperative CRP levels are related to an increased risk of PPH C.

We will present the results of several experiments used to characterize the properties and performance of multiple baseball bats composed of four different species of wood including soft maple, hard maple, birch, and ash. Resonant ultrasound spectroscopy was used in an effort to obtain the complete orthotropic tensor of the different wood species. In addition, ultrasonic pulse-echo measurements and dynamic impulse time-of-flight measurements were performed to obtain longitudinal sound speeds, which in combination with bat geometry, mass, and density enabled the determination of the longitudinal Young’s moduli. Bat performance was then experimentally determined via a newly developed non-destructive impact method. The physical acoustic parameters that most significantly correlated with optimum bat performance will also be presented.

Background and aims: In general, previous studies on adjuvant chemotherapy have not included the elderly breast cancer (BC) population. Our aim was to investigate the actual recommended adjuvant therapy for patients' age ≥70 years in clinical routine. We also determined the proportion of patients that terminated therapy in correlation to documented BC relapses. Material and Methods: Charts from consecutive patients diagnosed with a primary stage I-III BC from 1st January 2005 through 31st December 2007, age ≥70 years were studied (n = 358). Data regarding standard BC parameters at diagnosis, adherence to recommended adjuvant therapy, reasons for suspension of treatment and outcome were documented. Comparisons were performed with patients divided into three age groups (70–74; 75–79; and ≥80 years) and between different treatment modalities (i.e. endocrine therapy; chemotherapy; trastuzumab). Results: Higher age was statistically significantly correlated with axillary metastases (70–74y n=30, [30%]; 75–79 n=41, [49%]; and ≥80y n=120 [42%], (p = 0.011), while tumor size were equal (p = 0.103). No difference was found regarding routine BC parameters as histological type (p = 0.636) or grade (p = 0.662); vascular invasion (p = 0.681); ER (p = 0.892); PgR (p = 0.718) or HER2 status (p = 0.542). A total of 286 patients were advised adjuvant systemic therapy; only two patients received trastuzumab. A higher proportion of the oldest patients ≥80 (n = 32 [22%]) were left without any treatment compared with 75–79y (n = 17 [17%] and 70–74y (n = 13 [13%], (p = 0.0002), this was explained by differences regarding chemotherapy. Data on compliance was lacking for five patients, however there was a trend not reaching statistically significance revealing a correlation between higher age and a more frequent treatment termination (p = 0.061). Treatment suspension was for chemotherapy (70–74y n=21, [52%]; 75–79 n=17, [71%]; and ≥80y n=3 [100%] and for ET (70–74y n=69, [25%]; 75–79 n=66, [32%]; and ≥80y n=104 [46%]. There was a statistically significant correlation between higher age and more breast cancer relapses (BCR) (p = 0.015) and RFS (p = 0.038). We found a higher proportion of BCR among patients terminating planned treatment (n = 112; 27% BCR) compared with patients adherent to therapy (n = 168; 8% BCR) (p = 0.015). Patients not recommended any treatment (n = 62) had an intermediate outcome with 16% BCR. This observation was found in all age groups; patients terminating therapy; 70–74y 21% BCR, 75–79y 42% BCR and ≥80y 20% BCR respectively compared with patients' adherent to therapy 70–74y 6% BCR, 75–79y 10% BCR and ≥80y 7% respectively. Conclusions: Elderly patients are diagnosed with BC at a later stage and adjuvant chemotherapy, as well as, endocrine therapy prematurely terminated. Insufficient treatment was significantly associated with increased risk of relapse. Less toxic regimens should be carefully investigated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-12-01.

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

The arteriovenous graft (AVG) is most often used in hemodialysis patients when an autogenous fistula is not feasible. The optimal location (forearm or upper arm) and configuration (loop or straight) of AVGs are not known. To evaluate relationships of AVG location and configuration with patency, we conducted a secondary analysis using data from a randomized, placebo-controlled trial of dipyridamole plus aspirin for newly placed AVG.Participants of the Dialysis Access Consortium (DAC) Graft Study with newly placed upper extremity prosthetic grafts involving the brachial artery were studied. Multivariable analyses adjusting for trial treatment group, center, gender, race, body mass index, diabetes, current treatment with chronic dialysis, and prior arteriovenous vascular access or central venous catheter were performed to compare outcomes of forearm (fAVG) and upper arm (uAVG) grafts, including loss of primary unassisted patency (LPUP) and cumulative primary graft failure (CGF). Subgroup analyses of graft configuration and outflow vein used were also conducted.A total of 508 of the 649 participants (78%) enrolled in the trial had an upper extremity brachial artery graft placed, 255 with fAVG and 253 with uAVG. Participants with fAVG were less often male (33% vs 43%; P = .03), African American (62% vs 78%; P .001), and receiving dialysis at the time of surgery (62% vs 80%; P .001). Participants with fAVG had a higher mean body mass index (33 vs 29; P .001). The LPUP (fAVG 70% vs uAVG 78%; P = .07) and CGF (33% vs 36%; P = .91) were similar between fAVG and uAVG at 1-year follow-up. In multivariable analysis, AVG location (uAVG vs fAVG) was not associated with LPUP (hazard ratio, 1.21; 95% confidence interval, 0.90-1.63; P = .20) or CGF (hazard ratio, 1.36; 95% confidence interval, 0.94-1.97; P = .10). LPUP did not differ significantly between fAVG and uAVG among subgroups based on AVG configuration (P = 1.00) or outflow vein used (P = .16).Patency was comparable between fAVG and uAVG despite the larger caliber veins often encountered in the upper arm in carefully selected patients. Our findings support the traditional view that, in order to preserve a maximal number of access sites, the forearm location should be considered first before resorting to an upper arm graft.

Background Heavy drinking in early adulthood among Blacks, but not Whites, has been found to be associated with more deleterious health outcomes, lower labor market success and lower educational attainment at mid-life. This study analysed psychosocial pathways underlying racial differences in the impact of early heavy alcohol use on occupational and educational attainment at mid-life. Methods Outcomes in labor market participation, occupational prestige and educational attainment were measured in early and mid-adulthood. A mixture model was used to identify psychosocial classes that explain how race-specific differences in the relationship between drinking in early adulthood and occupational outcomes in mid-life operate. Data came from Coronary Artery Risk Development in Young Adults, a longitudinal epidemiologic study. Results Especially for Blacks, heavy drinking in early adulthood was associated with a lower probability of being employed in mid-life. Among employed persons, there was a link between heavy drinking for both Whites and Blacks and decreased occupational attainment at mid-life. We grouped individuals into three distinct distress classes based on external stressors and indicators of internally generated stress. Blacks were more likely to belong to the higher distressed classes as were heavy drinkers in early adulthood. Stratifying the data by distress class, relationships between heavy drinking, race and heavy drinking–race interactions were overall weaker than in the pooled analysis. Conclusions Disproportionate intensification of life stresses in Blacks renders them more vulnerable to long-term effects of heavy drinking.

Nemaline myopathy (NM) is a disorder of the skeletal muscle thin filament characterised by muscle dysfunction and electron-dense protein accumulations (nemaline bodies). Pathogenic mutations have been described in nine genes to date, but the genetic basis remains unknown in many cases. We used whole exome sequencing (WES) in two families with NM and subsequent gene sequencing in over 540 additional genetically unresolved NM patients to identify and characterise a new genetic cause of NM. We developed a knock-down zebrafish model of this condition and used immunohistochemistry, western blotting, single-fibre contractility studies and recombinant protein studies to characterise the expression, localisation and biochemical functions of the new disease-related protein. We identified homozygous or compound heterozygous variants in LMOD3, which encodes leiomodin-3 (Lmod3) in 21 patients from 14 families. Affected individuals had severe generalised weakness and hypotonia, and most affected individuals died in the neonatal period. We demonstrated that Lmod3 is expressed from early muscle differentiation, localises to thin filaments with enrichment at the pointed ends, and has strong actin nucleating activity. Loss of Lmod3 in patient muscle results in shortening and disorganisation of thin filaments. Knockdown of lmod3 in the zebrafish replicates this phenotype. These findings define a new genetic subtype of congenital myopathy and demonstrate an essential, previously unrecognised role for Lmod3 in the regulation of sarcomeric thin filaments in skeletal muscle.

Purified nicotinamide nucleotide transhydrogenase from beef heart was investigated with respect to labeling and subsequent sequence analysis of a nicotinamide nucleotide-binding site. A photo-activated azide derivative, 8-azidoadenosine 5′-monophosphate, was used as an active-site-directed photoaffinity label, which was shown to be specific for the NAD(H)-binding site in the dark. Light-activated incorporation of the label in transhydrogenase was accompanied by an inactivation, which approached 100% at the incorporation of about 1 mol label/mol transhydrogenase monomer. As expected from the assumed site-specificity of the label, NADH prevented both labeling and inactivation to some extent. However, NADPH also prevented labeling and inactivation marginally. The oxidized substrates NAD + and NADP + were inhibitory by themselves under these conditions, and the substrate analogs 5′-AMP and 2′-AMP were also poor protectors. The NAD(H)-site specificity of the azido compound was thus largely lost upon illumination and covalent modification. Radioactive labeling of transhydrogenase with 8-azido-[2- 3 H]-adenosine 5′-monophosphate followed by protease digestion, isolation of labeled peptides and amino-acid sequence analysis showed that Tyr 1006 in the sequence 1001–1027 close to the C-terminus was labeled. This sequence shows homologies with nucleotide-binding sequences in, e.g., F 1 -ATPase. On the basis of sequence homologies with other NAD(P)-dependent enzymes it is proposed that transhydrogenase contains 4 nucleotide-binding sites, of which 2 constitute the adenine nucleotide-binding domains of the catalytic sites for NAD(H) and NADP(H) close the the N- and C-terminals, respectively. Each of these domains has an additional vicinal nucleotide-binding sequence which may constitute a non-catalytic nucleotide-binding site or the nicotinamide nucleotide-binding domain of the catalytic site. The present results indicate that 8-azidoadenosine 5′-monophosphate is kinetically specific for the catalytic NAD(H)-binding site, but reacts covalently with Tyr 1006 of the putative non-catalytic site or nicotinamide nucleotide-binding domain formed by the 1001–1027 amino acid sequence of the catalytic NADP(H)-binding site. Interactions between the catalytic NAD(H) and NADP(H) binding sites, and the assumed non-catalytic sites, may be facilitated by a ligand-triggered formation of a narrow pocket, which normally allows an efficient hydride ion transfer between the natural substrates.

To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management.National, population-based, prospective registry data were used, including comprehensive 5-year follow up of 3783 patients operated on in the period 1998-2000. Local recurrence rates were compared using crude rate, Kaplan-Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed.The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed.We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

The cytoplasmic domain of the human erythrocyte anion exchanger 1 (cdAE1) serves as a center of organization for the red blood cell cytoskeleton as well as several metabolic enzymes and hemoglobin. The protein is known to undergo a reversible pH-dependent conformational change characterized by a 2-fold change in the intrinsic fluorescence and an 11 A change in the Stokes radius. While the exact changes in the molecular structure are unknown, on the basis of the crystal structure of the protein at pH 4.8 and site-directed mutagenesis studies, Zhou and Low (19) have proposed that the peripheral protein binding (PPB) domain of cdAE1 moves away from the dimerization domain in response to increasing alkalinity. To test this hypothesis, we have applied luminescence resonance energy transfer (LRET) to measure the intermonomer distance between donor and acceptor probes at the Cys201 site (located in the PPB domain) within the cdAE1 dimer. This distance was found to increase as the pH is increased from 5 to 10, in recombinant forms of both the wild type and a mutant (C317S) of cdAE1. Furthermore, LRET measurements in red blood cell inside-out vesicles indicate that when cdAE1 is linked to the membrane, the intermonomer distance is larger at pH 5, compared to that of the purified cdAE1 segments, and exhibits a different pH-dependent behavior. An increase in the distance was also observed on binding of a metabolic enzyme, glyceraldehyde-3-phosphate dehydrogenase, to cdAE1. These data provide the first demonstration of a defined change in the molecular structure of cdAE1, and also indicate that the structure under physiological conditions is different from the crystal structure determined at low pH.

GFAP levels in the CSF were highly elevated in three genetically confirmed cases of Alexander disease clinically conforming with infantile, early and late juvenile forms. No other CSF abnormalities were detected. Assay of CSF-GFAP may prove to be a rapid and cost-effective screening test in clinical variants of Alexander disease and an indicator of GFAP gene mutations.

High-dose therapy has become a common treatment for myeloma. The objectives of this study were to estimate in a prospective, population-based setting the impact on survival of high-dose therapy in newly diagnosed, symptomatic patients less than 60 years old and to compare the results with those of conventionally treated historic controls. The prospective population comprised 348 patients. Of these, 274 were treated according to a specified intensive-therapy protocol (Nordic Myeloma Study Group [NMSG] #5/94) and constituted the intensive-therapy group. The historic population consisted of 313 patients identified from 5 previous population-based Nordic studies. Of these, 274 fulfilled the eligibility criteria for high-dose therapy stated in NMSG #5/94 and constituted the control group. The expected numbers of patients in the prospective population and the historic population were 450 and 410, respectively, estimated from previously established data on the incidence in this population and the population base for each study. Survival was prolonged in the intensive-therapy group compared with the control group (risk ratio for the control group 1.62; 95% confidence interval 1.22-2.15; P =.001). These groups represented more than 60% of the expected number of patients. When survival for all the registered patients in the 2 populations was compared, representing more than 75% of the expected number of patients, the advantage for the prospective population persisted (risk ratio for the historic population 1.46; 95% confidence interval 1.14-1.86; P =. 002). These results indicate that the introduction of high-dose therapy for newly diagnosed myeloma has resulted in prolonged survival for the total patient population aged less than 60 years. (Blood. 2000; 95:7-11)

We have analysed the prognostic information for survival of presenting features in an unselected series of 394 myeloma patients. 15 variables with significant prognostic information were identified, among these were some not previously or only recently reported: serum levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), C-terminal cross-linked telopeptide of collagen I (ICTP) and soluble interleukin-6 receptor (sIL-6R). In a multivariate Cox analysis six variables were significantly and independently associated with poor survival: high age, low W.H.O.-performance status (PS), high serum levels of calcium, beta-2-microglobulin (beta-2M), IL-6 and sIL-6R. A risk score formed to predict survival for each percentile of the patient population allowed an efficient separation of prognostic groups. The discriminating power of the model compared favourably with three other previously published staging systems applied to the study population. Exclusion of IL-6 and sIL-6R from the model only marginally decreased the efficacy of the separation. The predictive value of some variables (sIL-6R, beta-2M and W.H.O.-PS) decreased significantly over time. We conclude that formation of a risk score based on independent variables is an efficient way to separate prognostic groups, that the contribution of new and not easily available parameters should be thoroughly evaluated before inclusion in prognostic models for clinical use and that the predictive value of parameters may decrease over time.

When a randomized trial (NMSG 4/90) comparing treatment with melphalan/prednisone to melphalan/ prednisone + interferon alpha-2b in newly diagnosed multiple myeloma was initiated in 1990, a quality-of-life assessment was integrated into the study. We used the questionnaire (QLQ-C30) developed by the European Organization of Research and Treatment of Cancer (EORTC) Study Group on Quality of Life. The QLQ-C30 incorporates five functional scales, three symptom scales, a global health and quality-of life scale and some single symptom measures. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 524 (90.2%) of 581 patients enrolled in the NMSG 4/90 completed the first questionnaire, and 484 (83.3%) completed all questionnaires given to them. All but one of the scales met the minimum criteria of reliability (Cronbach's alpha/ 0.70). Validity was shown by (1) the ability of the scales to discriminate clearly between patients differing in clinical status as defined by pretreatment W.H.O. performance index and DurieSalmon stage, and (2) the sensitivity to changes in objective disease status (response and relapse). This is the first report of the measurement of health-related quality of life in a prospective clinical trial in multiple myeloma. The results demonstrate that the QLQ-C30 is a reliable and valid instrument for the measurement of quality of life in these patients. The data will be used for a cost-utility analysis of the results of the NMSG 4/90 trial.

Nicotinamide nucleotide transhydrogenase (E.C. 1.6.1.1) from Escherichia coli was investigated with respect to the role of specific conserved tyrosine residues of putative substrate-binding regions. The enzyme from E. coli is made up of two subunits, a (510 residues) and 8 (462 residues). The corresponding enzyme from bovine mitochondria is a single polypeptide (1043 residues) whose N-terminal region corresponds to the a subunit and whose C-terminal region corresponds to the ,!3 subunit. Tyrosines 245 and 1006 of the mitochondrial enzyme have been shown to react selectively with 5'-@-fluorosulfonylbenzoyl)adenosine with inactivation of the enzyme. In E. coli these residues correspond to tyrosine 226 of the a subunit and tyrosine 431 of the B subunit. In addition, tyrosine 315 of the @ subunit is of interest since mutation of an adjacent residue (glycine 314 ) leads to inactivation (Ahmad, S., Glavas, N. A,, & Bragg, P. D. (1992) Eur. J. Biochem. 207, 733-7391. In order to assess the role of the aforementioned conserved tyrosine residues in the mechanism and structure of transhydrogenases, these were replaced by site-specific mutagenesis, using the cloned and overexpressed E. coli transhydrogenase genes (Clarke, D. M., & Bragg, P. D. (1985) J. Bucteriol. 262, 367-3731. Phenylalanine mutants of all three tyrosine residues showed approximately 50% activity or more with regard to catalytic activity assayed as reduction of 3-acetylpyridine-NAD+ by NADPH. These mutants were also active in proton pumping assayed as quenching of 9-methoxy-6-chloro- 2-aminoacridine or quinacrine fluorescence. With respect to catalytic activity these and other mutants were ranked as aY226F > L = H > N, BY431F >> L = H = N = I, and BY315F > N = H > L > D = I = V, indicating that the amino acids at position 226 of the a-subunit and positions 431 and 3 15 of the 8-subunit should be aromatic and sufficiently large and hydrophobic or hydrophilic, but not charged or small (aliphatic) and hydrophobic. These results suggest that tyrosine 226 of the a subunit, and tyrosines 43 1 and 31 5 of the B subunit are not essential for catalytic activity or proton pumping.

Two dietary reporting methods were used to examine associations between macronutrient intake and subsequent cancer incidence in a cohort of Swedish women born between 1908 and 1930. 1361 subjects gave 23-h dietary recalls at their baseline examinations in 1968-1969, and 412 of them also provided detailed dietary histories. The cohort was followed up 19 years later by means of linkages with the National Cancer and Death Registries. Both dietary methods indicated that subjects who were ranked in the highest tertile of energy intake, relative to the lowest, were at significantly greater risk of developing cancer (all-site). Relative risks across energy intake tertiles were 1, 1.15 and 2.04, respectively, using the dietary history method and 1, 1.02 and 1.55 using the 24-h recall data. Examination of specific macronutrient energy sources indicated that dietary fat and carbohydrate are likely to have made the largest contribution to this association. However, after adjustment for total energy, none of the individual macronutrients was significantly associated with all-site cancer, by either dietary reporting method. When expressed as a percentage of total energy, low protein density of the diet was associated with increased cancer risk, by both dietary methods. However, this appeared to be a function of high energy intake rather than low protein intake. Simultaneous statistical adjustment for seven potential confounders of the association between energy intake and cancer was performed using both the 24-h recall and the dietary history data.(ABSTRACT TRUNCATED AT 250 WORDS)

To find out if there is an association between DNA indexes and DNA synthesis (S) phase measurements and Dukes' classification and histopathological differentiation in colorectal cancers, and to investigate the interrelationship between DNA indexes and S phase measurements.Prospective open study.182 colorectal carcinomas in 181 consecutive patients.Tumours biopsied immediately after resection or at rectoscopy or colonoscopy.One or more aneuploid cell populations were found in 113 of 182 carcinomas (62%). There was no correlation between Dukes' stage and either degree of differentiation or S phase measurements, but there were significant correlations between S phase measurements and histological grading (p less than 0.05), and between the percentage of cells in the S phase and the DNA index when values for both diploid and aneuploid tumours were included (p less than 0.001).The degree of aneuploidy indicates how far tumour cells have progressed in their cellular disarrangement, and information about a tumour's proliferative capacity is given by the S phase measurements.

During the 3 years 1984-86, 314 cases of multiple myeloma were diagnosed in the Health Care Region of Western Sweden. 180 of these cases were included in a clinical trial; 71 were notified to the trial but excluded; 49 cases were not reported to the trial; 14 were diagnosed post mortem. The crude incidence rate of myeloma was 6.3 cases per 100,000 inhabitants per year, corresponding to an age-adjusted (world standard population) incidence rate of 2.9 cases per 100,000 inhabitants per year. The excluded and the non-reported patients had a significantly shorter survival than those included in the clinical trial (median survival 22, 13 and 33 months, respectively). This was partly due to differences in age and proportion of actively treated patients between the groups, but the same tendency remained also after correction for these factors. Considering the included patients separately, the effect of tentative application of presumptive exclusion criteria corresponding to major prognostic factors was studied. Prolonged survival was seen when the upper age limit was lowered and when patients with renal failure or low performance status were excluded. The results illustrate the fact that for multiple myeloma the survival in a trial population is markedly influenced by active and passive exclusion of patient groups with unfavourable prognostic characteristics. When reporting results of clinical trials, discussion of the representativeness of the trial population for the total patient population is recommended in order to facilitate application of the trial results to medical practice and comparisons between trials.

From October 1983 until December 1986, 164 patients with multiple myeloma stage II-III were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) with multidrug chemotherapy (MDC). The patients comprised 77% of all newly diagnosed myeloma stage II-III cases reported from 18 hospitals covering the entire Health Care Region of Western Sweden (1.5 million inhabitants). Patients randomized to MP (29 stage II and 55 stage III patients) were given oral melphalan and prednisone every 6 weeks. For patients randomized to MDC, stage II patients (n = 25) were given VMCP every 4 weeks and stage III patients (n = 53) VBAP and VMCP alternately every 4 weeks. For stage II patients, the response rate for MP compared to VMCP was 69 versus 56% and the median survival 46 versus 33 months. For stage III the response rate for MP compared to VBAP/VMCP was 58 versus 57% and the median survival 26 versus 24 months. No statistically significant differences were seen. The time to response and remission duration were also similar in both treatment arms. The dose intensity index (cumulative given/planned dose of myelosuppressive drugs) was greater than or equal to 0.8 in 89% of the MP patients and 81% of the MDC patients. Patients with index values less than 0.8 had the same response rate as patients with index greater than or equal to 0.8. This study has not demonstrated any advantage of MDC over traditional MP in multiple myeloma stage II-III.

T HESE TWO INTRODUCTORY EPIGRAPHS, Victorian and native American, indicate the cross-cultural and trans-historical consistency of the connection between spiders' webs and narrative.2 While the first author is broadly concerned with the problematics of gender and creative productivity, especially literary productivity, the second specifically asserts a feminine author or creator for the web of narrative. The basis for the presence of spiders and their webs in both of these considerations of narrative can be found in the long-standing association between notions of weaving and the creation of narrative, an association occasionally expressed through arachnid imagery.3 Furthermore, because of the traditional cultural role which women occupy as weavers, any weaving metaphor, simile, or analogy which is employed for narrative is already implicated in issues of gender. This relationship between women and weaving is made explicit in Silko's version of the beginning of things, where a female spider is responsible for the naming, and thus the creation, of both reality and fiction. In this native American myth, not only is a female (spider) credited with the tangible activity of weaving, but also with the intangible, abstract production of narrative. Woolfs words leave latent the connection between the feminine and the weaving of narratives, yet

Previous workers have determined that the ${\mathrm{Ag}}^{0}$ center produced in alkali halides doped with silver and $\ensuremath{\gamma}$ or x irradiated at 77 K is a silver atom in a substitutional cation site. Through the use of electron-nuclear double resonance (ENDOR) we have measured the hyperfine parameters of the first four neighbor shells about this ${\mathrm{Ag}}^{0}$ center at 4 K in KCl and NaCl. Contrary to a suggestion made in an earlier study, no indication was found of a lattice vacancy near the ${\mathrm{Ag}}^{0}$ center. For both crystals there was an anomalously high contact interaction with shell-4 nuclei. Quadrupole-interaction constants were in most cases quite different from those expected through consideration only of the effect of the extra electron at the silver lattice site. This difference probably is an indication of lattice distortion about the ${\mathrm{Ag}}^{0}$ center. Extra structure which appeared in first-shell ENDOR spectra in both crystals was successfully accounted for as second-order hyperfine structure. Fabrication of the superhyperfine structure of the high-field ESR line from ENDOR parameters yielded good agreement for KCl but showed that not all of the ESR line broadening could be accounted for by interactions with the first four shells for the ${\mathrm{Ag}}^{0}$ center in NaCl.

At 4.2 K EPR absorption by Ni2+ in a substitutional octahedral site in AgCl:Ni results in a broad line at g=2.276. For high microwave powers, a narrow line with resolved superhyperfine structure appears at the same g value. This narrow line is attributed to a double quantum transition by the Ni2+ ion. Superhyperfine coupling parameters to the nearest neighbor chloride ions are derived by fitting the narrow line. The covalent bonding parameters for NiCl4−6 are calculated to be fs=0.67% and fσ=6.79% by means of the independent bonding model.

Based on the studies of the thermal stability and the oxidizing annealing at 1350 °C, it is concluded that the one-hole center observed in a 300 K γ-irradiated Al2O3 crystal is predominantly the VOH- center. The OH− ions can be removed from the Al2O3 crystal by prolonged annealing in air at 1350 °C. The emission spectra show that the γ-ray induced thermoluminescence peaks at 390, 420, 440, 500, and 550 K peaks observed in oxidized and non-oxidized Al2O3 crystal are all related to the R-lines emission from Cr3+ in Al2O3. The 390, 420, and 500 K peaks result from thermal destruction of the hole centers by hole release. The 550 K peak is caused by the restoration of unperturbed, substitutional Cr3+ ions. Auf Grund von Untersuchungen der thermischen Stabilitat und von Oxydationstempern bei 1350 °C wird gefolgert, das das Loch-Zentrum, welches in einem bei 300 K γ-bestrahlten Al2O3-Kristall beobachtet wird, vorwiegend das VOH−-Zentrum ist. Die OH--Ionen konnen durch ausreichend langes Tempern in Luft bei 1350 °C aus dem Al2O3-Kristall entfernt werden. Die Emissionsspektren zeigen, das die durch Gammastrahlen erzeugten Thermolumineszenzmaxima bei 390, 420, 440, 500, und 550 K, die im oxydierten und nicht-oxydierten Al2O3-Kristall beobachtet werden, alle mit den R-Emissionslinien von Cr3+ in Al2O3 in Zusammenhang stehen. Die 390-, 420- und 500 K-Maxima resultieren aus der thermischen Zerstorung der Loch-Zentren durch Abgabe der Locher. Das 550 K-Maximum wird durch die Wiederherstellung ungestorter, substitutioneller Cr3+-Ionen erzeugt.

Experience in the petroleum industry shows there are other factors besides tensile, creep, and stress rupture to consider in the use of austenitic steels in high-temperature service. There is no advantage in using stabilized grades in many applications. A spheroidizing heat-treatment is generally effective where stabilized steel is required. The coefficient of expansion and the thermal conductivity have been important factors in thermal-shock and thermal-fatigue failures in austenitic steels.

Azeotropes of CH/sub 3/COOH and CH/sub 3/COOD with pyridine, trimethylamine, and triethylamine have been prepared The boiling point differences between the H and D forms of the azeotropes are larger than those between the isotopic forms of pure acetic acid. The composition and some physical properties of the azevtropes have been determined. Upon distillation of the azoatropes, there is some separation of the nitrogen isotopes and possibly, also of the carbon and oxygen isotopes of the carboxyl group in the acetic acid. (auth)