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IntroductionWith the pressing need to develop treatments that slow or stop the progression of Alzheimers disease, new tools are needed to reduce clinical trial duration and validate new targets for human therapeutics. Such tools could be derived from neurophysiological measurements of disease. Methods and AnalysisThe New Therapeutics in Alzheimers disease study (NTAD) aims to identify a biomarker set from magneto/electro-encephalographic that is sensitive to disease and progression over one year. The study will recruit 100 people with amyloid-positive mild cognitive impairment or early-stage Alzheimers disease and 30 healthy controls aged between 50 and 85 years. Repeat measurements of the clinical, cognitive and imaging data (magnetoencephalography, electroencephalography and magnetic resonance imaging) of participants with Alzheimers disease or mild cognitive impairment will be taken at baseline and at one year. To assess reliability of magneto/electro-encephalographic changes, a subset of 30 participants with mild cognitive impairment or early-stage Alzheimers disease will undergo repeat magneto/electro-encephalographic two weeks after baseline. Clinical and cognitive assessment will be repeated at 2 years. Linear mixed models of baseline and longitudinal change in neurophysiology are the primary analyses of interest, supported by Bayesian inference. Additional outputs will include relative effect sizes for physiological markers, atrophy and cognitive change and the respective numbers needed to treat each arm of simulated clinical trials of a future disease modifying therapy. Ethics and disseminationThe study has received a favourable opinion from the East of England Cambridge Central Research Ethics Committee (REC reference 18/EE/0042). Results will be disseminated through internal reports, peer-reviewed scientific journals, conference presentations, website publication, submission to regulatory authorities and other publications. Data will be made available via the Dementias Platform UK Data Portal on completion of initial analyses by the NTAD study group. STRENGTHS AND LIMITATIONS OF THIS STUDYO_ST_ABSStrengthsC_ST_ABSO_LINTAD is a longitudinal, multicentre study of magneto/electro-encephalographic measures of Alzheimers disease progression C_LIO_LINTAD assesses the test-retest reliability of magneto/electro-encephalographic parameters C_LIO_LIAll participants with early-stage Alzheimers disease or mild cognitive impairment will be amyloid-positive C_LI LimitationsO_LIAttrition during follow up may limit inferences C_LIO_LIRecruitment is from volunteer panels and clinical services that may not reflect national diversity of people affected by Alzheimers disease C_LI

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.

Women are dramatically underrepresented in legislative bodies, and most scholars agree that the greatest limiting factor is the lack of female candidates (supply). However, voters’ subconscious biases (demand) may also play a role, particularly among conservatives. We designed an original field experiment to test whether messages from party leaders can affect women's electoral success. The experimental treatments involved messages from a state Republican Party chair to the leaders of 1,842 precinct-level caucus meetings. We find that party leaders’ efforts to stoke both supply and demand (and especially both together) increase the number of women elected as delegates to the statewide nominating convention. We replicate this finding in a survey experiment with a national sample of validated Republican primary election voters (N = 2,897). Our results suggest that simple interventions from party leaders can affect the behavior of candidates and voters and ultimately lead to a substantial increase in women's descriptive representation.

Studies of representation have focused primarily on the correlation between legislators’ voting records and their constituents’ preferences; however, accountability inevitably includes representatives’ explanations of their legislative actions. Unlike previous research that has examined consistency within a single form of communication, this study systematically examines legislators’ consistency in the explanations they give across different means of communication. Contrary to arguments that members of Congress do not vary their explanations or presentational styles, we find that incumbents present themselves to constituents differently through different methods of communication. Using the 2006 Campaign Communication Survey, a random survey of registered voters in Ohio and Pennsylvania who were asked to send in all campaign mail received during three weeks in 2006, we compare the content of campaign mail and franked mail incumbents send to constituents. Even though the mediums of communication are similar...

Objective To report the effect of bevacizumab versus dexamethasone on hard exudates (HEX) in diabetic macular oedema (DME). Design Post hoc analysis of 24-month data from the Randomised clinical trial of BEVacizumab OR DEXamethasone for diabetic macular oedema (BEVORDEX) phase 2 multicentre randomised clinical trial. Eyes with centre-involving DME resistant to or unlikely to benefit from macular laser therapy were included. Eyes were randomly assigned to bevacizumab every 4 weeks or Ozurdex dexamethasone implant (DEX) every 16 weeks, both as required. The 68 eyes from 48 patients that completed 24-month follow-up were analysed. Two masked graders assessed extent and location of HEX on baseline, 12-month and 24-month foveal-centred colour fundus photographs using validated grading software. Results Macular HEX was present in 60% of study eyes. Of these, 21 eyes were treated with DEX and 20 eyes with bevacizumab. Both treatments led to reduction in area of macular HEX at 12 months and 24 months. There was greater regression of HEX from the foveal centre in DEX-treated eyes (median change +890 µm, IQR=1040 µm) than bevacizumab-treated eyes (median change +7.0 µm, IQR=590 µm) at 12 months (p=0.04) but the difference was no longer statistically significant (p=0.10) by 24 months (DEX +1400 µm, IQR=1590 µm; bevacizumab +20 µm, IQR=2680 µm). Reassuringly, no study eye developed HEX at the foveal centre, a visually devastating consequence of diabetic maculopathy. Conclusions Bevacizumab and DEX were effective in reducing area of HEX in eyes with DME. DEX provided more rapid regression of HEX from the foveal centre although bevacizumab-treated eyes started to catch up by 24 months. Distance from the foveal centre as well as total area of macular HEX should be assessed when evaluating treatments for foveal-threatening HEX. Trial registration number NCT01298076; Post-results.

Despite consensus regarding the civic shortcomings of American citizens, no such scholarly consensus exists regarding the effectiveness of civic education addressing political apathy and ignorance. Accordingly, we report the results of a detailed study of students enrolled in introductory American politics courses on the campuses of two large research universities. The study provides pre- and postmeasures for a broad range of political attitudes and behaviors and includes additional long-term observations in survey waves fielded 6, 12, and 18 months after the conclusion of the class. Long-term observation provides leverage absent in many prior studies and enables us to compare the changes we observe during the semester to those that take place beyond the confines of the classroom and during important political events, such as the 2012 presidential election. Also embedded in the study is an experiment designed to assess whether students’ enthusiasm for “new media” (e.g., blogs) can be harnessed in American...

Objective To report the 12-month results of the first head-to-head comparison of a dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, CA) versus bevacizumab (Avastin; Genentech, South San Francisco, CA) for center-involving diabetic macular edema (DME). Design Phase 2, prospective, multicenter, randomized, single-masked clinical trial (clinicaltrials.gov identifier NCT01298076). Participants We enrolled 88 eyes of 61 patients with center-involving DME. Methods Forty-two eyes were randomized to receive bevacizumab every 4 weeks and 46 eyes were randomized to receive a dexamethasone implant every 16 weeks, both pro re nata. Results were analyzed using linear regression with generalized estimation equation methods to account for between-eye correlation. Main Outcome Measures The primary outcome was the proportion of eyes that improved vision by 10 logarithm of minimum angle of resolution letters. Secondary outcomes included mean change in best-corrected visual acuity (BCVA), change in central macular thickness (CMT), injection frequency, and adverse events. Patient-reported outcomes were measured using the Impact of Vision Impairment (IVI) questionnaire. Results Improvement in BCVA of 10 or more letters was found in 17 of 42 eyes (40%) treated with bevacizumab compared with 19 of 46 dexamethasone implant–treated eyes (41%; P = 0.83). None of the 42 bevacizumab eyes lost 10 letters or more, whereas 5 of 46 (11%) dexamethasone implant eyes did, mostly because of cataract. Mean CMT decreased by 122 μm for bevacizumab eyes and by 187 μm for dexamethasone implant eyes ( P = 0.015). Bevacizumab-treated eyes received a mean of 8.6 injections compared with 2.7 injections for dexamethasone implant eyes. Significant improvement in IVI scores occurred for both treatment groups. Conclusions Dexamethasone implant achieved similar rates of visual acuity improvement compared with bevacizumab for DME, with superior anatomic outcomes and fewer injections. Both treatments were associated with improvement in visual quality-of-life scores. However, more dexamethasone implant–treated eyes lost vision, mainly because of cataract.

Background Diabetic macular oedema (DMO) is the commonest cause of vision loss in people with diabetes. Laser photocoagulation can be effective in the treatment of DMO; however, its mechanism of action is still poorly understood. A better understanding of these mechanisms may allow the development of therapeutic approaches that could avoid the deleterious adverse events associated with photocoagulation. Methods We have used proteomic techniques to identify the protein changes induced by threshold intensity retinal laser treatment in a rodent model of diabetic retinopathy. Retinae were obtained from diabetic Dark Agouti rats 8 weeks following laser treatment. Extracted proteins from lasered and non-lasered diabetic retinae were separated and compared using two-dimensional gel electrophoresis. Results Image analysis revealed 24 protein spots with decreased expression after laser treatment and 9 spots with increased expression. On lasered retinal gels, four spots were uniquely expressed, with eight unique spots on non-lasered gels. Twenty-two protein spots of interest were identified using matrix-assisted desorption ionization-mass spectrometry with database matching. Following laser, Wnt-5 beta, LEK-1, GADPH, claudin-12 and calretinin were significantly down-regulated in expression. Conclusions The present study provides a proteomic insight into the underlying biological basis for the therapeutic effects of laser for DMO. We provide further evidence of the involvement of Wnt pathway signalling in the neural retina in DMO, and for up to 2 months following laser treatment. Changes in LEK-1 and claudin-12 may have effector roles, and changes in glyceraldehyde-3-phosphate dehydrogenase and calretinin may reflect the altered retinal microenvironment resulting from laser treatment.

Political campaigns raise millions of dollars each election cycle. While past research provides valuable insight into who these donors are and why they are motivated to give, little research takes into account the actions of political campaigns. This paper examines why and how campaigns target habitual donors for political donations. Using the 2004 Campaign Communication Survey, a national survey of registered voters who were asked to collect and send in all campaign mail they received during the last 3 weeks of a campaign, we show that campaigns send donation solicitations predominantly to individuals who have previously donated to a campaign. We also show that campaigns match targeting fundraising appeals to the potential motivations for giving: campaigns target the type of fundraising appeal they use, whether ideological, solidary, or material, to match the socioeconomic and partisan characteristics of the potential donor. The implication of effective targeting is that the “unequal” voice of participation in campaign contributions is not one-sided and simply resource based, but rather that campaigns also contribute to the situation with targeted messages to potential donors.

Most acute cases of central serous chorioretinopathy resolve spontaneously with minimal visual impairment. The small percentage of eyes developing chronic or recurrent disease that do warrant treatment is often difficult to control. Emergent investigations and treatments have added to the established options available to manage these cases. Optical coherence tomography has proved valuable for both imaging subtle fundoscopic findings and monitoring disease progression. Fluorescein angiography aids identification of pigment epithelial leaks and targets the use of argon laser treatment if outside the fovea. Fluorescein angiography also assists differentiation from other choroidal pathologies such as choroidal neovascularization and polypoidal choroidal vasculopathy. Where the diagnosis is uncertain, indocyanine green angiography can demonstrate classic midphase hyperpermeability. This is also useful to guide the application of photodynamic therapy. Newer treatments such as intravitreal anti-vascular endothelial growth factor are as yet unproven.

Central serous chorioretinopathy (CSCR) is a common retinal cause of vision loss. This review surveys the epidemiology, risk factors, clinical presentation, natural history and pathophysiology of CSCR. Studies suggest an annual incidence rate of 10 per 100 000 in men, with CSCR occurring six times more commonly in men compared with women. Most acute CSCR cases resolve spontaneously within 2-3 months. Prognosis is highly dependent on presenting visual acuity; patients with initial visual acuities of 6/6 remain at that level, while patients with initial visual acuities of less than 6/9 recover on average two to three Snellen lines over the next few years. The main risk factors for CSCR are systemic corticosteroid use, type A personality, pregnancy and endogenous Cushing's syndrome. The pathophysiology of CSCR remains obscure, although disorders in both the choroidal circulation and retinal pigment epithelium are implicated.

The scholarly literature provides mixed guidance on the question of whether DREs or optical scan systems inspire greater confidence. We bring new evidence to bear on the debate using a unique exit poll and a nationally representative survey, both of which examine a wide range of voting experiences. Having detailed information about voting experiences enables us to investigate both the direct effects of DRE/optical scan voting and the indirect effects through voting experiences. Doing so reveals new information about the relationships between voting technology, voting experiences, and voter confidence. Indeed, the type of machine one uses has very different direct and indirect effects on voter confidence—a finding that may help explain scholarly disagreement over voters’ reactions to different types of voting machines.

This study uses response latency, the time required for a survey respondent to formulate an answer upon hearing a question, to examine the accessibility of partisan self identifications over the course of a political campaign season. Although the aggregate distribution of partisanship remains fairly stable during the campaign, party identifications become more accessible to individuals with weaker party identifications as the election approaches. Consistent with theoretical expectations, the authors find that partisan orientations are more useful in forming political judgments when those orientations are more accessible to the voter. The effect of partisanship on vote choice is a third greater for voters with highly accessible party identifications than for those with less accessible party identifications.

The experiences in Florida in 2000 and Ohio in 2004 demonstrate that the election process can fall short of voters' expectations. In the wake of reforms, such as the Help America Vote Act (HAVA) of 2002, scholars have attempted to identify ways in which the objective conditions in polling places shape citizens' experiences and overall confidence in the electoral system. Early studies reveal that poll workers play a major role in the way voters feel about their voting experience. Using exit poll data on the delivery of service at the polling locations, we study the determinants of reactions to poll workers. We find poll worker evaluations are responsive to wait times, feelings of privacy while voting, poll worker training, and special poll worker recruiting efforts, to name a few. When voters feel good about their interactions with poll workers, they feel better about their voting experience and more confident about the electoral system.

Implementation of multicenter and/or longitudinal studies requires an effective quality assurance program to identify trends, data inconsistencies and process variability of results over time. The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study represent over 30 years of data collection among a cohort of participants across 27 clinical centers. The quality assurance plan is overseen by the Data Coordinating Center and is implemented across the clinical centers and central reading units. Each central unit incorporates specific DCCT/EDIC quality monitoring activities into their routine quality assurance plan. The results are reviewed by a data quality assurance committee whose function is to identify variances in quality that may impact study results from the central units as well as within and across clinical centers, and to recommend implementation of corrective procedures when necessary. Over the 30-year period, changes to the methods, equipment, or clinical procedures have been required to keep procedures current and ensure continued collection of scientifically valid and clinically relevant results. Pilot testing to compare historic processes with contemporary alternatives is performed and comparability is validated prior to incorporation of new procedures into the study. Details of the quality assurance plan across and within the clinical and central reading units are described, and quality outcomes for core measures analyzed by the central reading units (e.g. biochemical samples, fundus photographs, ECGs) are presented.

Diabetes is an increasingly common condition and hence, managing dying patients with diabetes as a co-morbidity will become a frequent challenge. It is uncertain whether there is net beneficence in preventing hyperglycaemia in diabetic patients during the terminal phase or whether the distress involved in administering therapy and blood glucose monitoring may outweigh this ordeal. Since there is no available evidence upon which to base clinical decisions, a semi-structured questionnaire based around three clinical vignettes was sent to consultants in diabetes and palliative care in the UK. There was consensus of opinion from both groups of consultants that treatment and monitoring should be stopped in patients with type 2 diabetes, once in the terminal phase. There was less consensus regarding management of type 1 diabetes. Practical issues were raised by both groups of consultants and clinical guidelines are suggested.

Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity.

Political apathy and ignorance are endemic among young people and many agree that improving civic education is tantamount to improving public awareness. How to go about inspiring engagement among young people, however, remains a topic of debate. For example, students who report on surveys that they were encouraged to express their political views in the classroom were also more politically engaged. But this might occur because students who were already engaged reported more opportunities to express political views. Spurious relationships could also occur because educators are more likely to undertake service learning, for example, when their students come from higher SES backgrounds. Experiments and long-term observation that could provide greater certainty about causal links have been rare. This paper presents results of a classroom-based experiment designed to assess whether students’ enthusiasm for “new media” (e.g. blogs) can be harnessed in American politics courses to stimulate long lasting political engagement.

The Prostate-Specific Antigen (PSA) and the Cancer-Associated Serum Antigen (CASA) assay for the MUC1 mucin were compared in the serum of 303 patients with malignant or benign prostatic disease. Using cutpoints of 4, 10, and 20 mu g/l, PSA was elevated in 93%, 81%, and 64% of patients with prostate cancer (n = 113), with corresponding specificities of 55%, 84%, and 96% in benign prostate disease (prostatic hyperplasia or prostatitis, n = 190). Using the recommended cutpoint of 4 Units/ml, CASA was elevated in 38% of patients with prostate cancer, with a specificity of 91% in benign disease. PSA and CASA showed a poor correlation in prostate cancer (r = 0.367) and benign disease (r = 0.158), and CASA was elevated in some PSA negative samples. Used together; PSA greater than or equal to 20 mu g/l and CASA greater than or equal to 4 kU/l gave perfect specificity in benign disease, with a corresponding sensitivity of 29% (positive and negative predictive values of 100% and 70%, respectively). However, this combination gave no improvement over the use of PSA alone, with sensitivity 47% when the cutpoint was raised to give perfect specificity. These data suggest that CASA is of little use as an adjunct to PSA in the differentiation of benign and malignant prostate disease.

OBJECTIVE To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. METHODS Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. RESULTS After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P < .001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P < .001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. CONCLUSION The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning. TRIAL REGISTRATION (clinicaltrials.gov) Identifiers: NCT00360815 and NCT00360893.

Many extrahepatic manifestations of hepatitis C have been described, including renal disease and vasculitis. We describe the novel finding of intimal hyperplasia associated with severe ischaemic events in two patients with hepatitis C. The combination of genotype 1a hepatitis C virus, rapidly progressive mesangiocapillary glomerulonephritis and intimal hyperplasia with ischaemic sequelae, may represent a new syndrome.

This is the first comparison of the three mucin based tests CA15-3, CASA, and MSA, and the cytokeratin-related TPS assay in breast cancer. The mucin markers were superior to TPS in receiver-operator analysis, though no marker was of use in the diagnosis of malignancy due to low sensitivity. Using cutpoints that gave 95% specificity in benign disease (n = 83), corresponding sensitivities in pre-treatment breast cancer (n = 123: 13 in situ, 54 stage I, 45 stage II, 4 stage III, 7 stage IV) were 17% (CA15-3), 16% (CASA), 13% (MSA), and 8% (TPS), with a strong relationship between marker levels and disease stage. These assays did not always detect the same patients, and the use of CA15-3 combined with CASA gave the highest sensitivity (23%), though this was not significantly better than the use of CA15-3 alone. Despite detecting similar antigens, these assays can show markedly different responses in some patients, indicating that one mucin-based test cannot be substituted for another.

The serum markers CA125, CASA and TPS were compared, with particular reference to the clinical applications of these tumor markers in the management of patients with ovarian cancer (discrimination of benign and malignant disease; indicating prognosis; predicting preclinical recurrence). (i) Using recommended cut-off points, CASA (greater than or equal to 4 U ml(-1)) and TPS (greater than or equal to 80 U l(-1))showed similar sensitivities in ovarian carcinoma (56% and 57% respectively), though these were lower than with CA125 (85% greater than or equal to 35U m l(-1)). The combined use of CA125 with either CASA or TPS at higher cut-off points excluding benign disease (CA125 >345 U ml(-1); CASA >6 U ml(-1); TPS>359 Ul(-1)) improved the discrimination of ovarian cancer from benign adnexal masses (100% positive predictive value with 65% of ovarian cancers detected with CA125-CASA, 61% with CA125-TPS vs 46% with CA125 alone). The combined preoperative use of these markers may therefore assist the general gynecologist in avoiding potentially difficult oncologic surgery. (ii) TPS was the best preoperative indicator of prognosis, possibly due to its association with cell proliferation, while CASA was superior as a postoperative prechemotherapeutic prognostic indicator, possibly due to it being a more accurate indicator of residual disease than the other markers, or the surgeons' assessment. Similarly, CASA gave the best differentiation of patients with minimal residual disease (

This paper argues that the viable systems model can be used by managers to understand and control their organizations.

In December 1993 the NSW Health Department was notified that two patients had presented with acute hepatitis C five and seven weeks after undergoing minor surgical procedures in the same operating session at a Sydney private hospital early that year. Neither case had other risk factors for acute hepatitis C.

Sera from 86 well controlled diabetics were examined for the presence of immune complexes. Thirty-six patients were receiving standard insulins, 19 monocomponent preparations, 24 oral hypoglycaemic agents and seven dietary restriction alone. Three methods were used to detect complexes: measurement of complement components, a Clq binding assay (BA) and the Raji cell radioimmunoassay (RIA). Complement components were normal in all patients. Eleven (31%) of the group on standard insulins had a positive Raji cell RIA; none had an abnormal Clq-BA. One patient on monocomponent therapy had a mildly positive Raji cell RIA; Clq-BA was negative in each patient of this group. Thirteen (54%) of the patients on oral hypoglycaemic agents were positive on one or both assays while one patient on diet alone was abnormal on both assays. These data show that immune complex production is common in both insulin-requiring and non-insulin-requiring diabetics and that this phenomenon is strikingly less frequent in patients on monocomponent insulins. Such observations could bear relevance to the pathogenesis of microvascular complications in diabetes.