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Background Radiotherapy (RT) is a mainstay in the treatment of glioma patients, but RT-resistance is common. We have recently identified RT-associated genomic small deletion signatures, marking tumors that have developed resistance. Here, we used longitudinal molecular profiles to explore non-genetic mechanisms of RT-resistance. Material and Methods We have analyzed the multi-omic Glioma Longitudinal Analysis (GLASS) dataset, integrating DNA and RNA sequencing datasets from primary and post-treatment gliomas. Results We classified tumors as harboring temozolomide-associated hypermutation based on mutational burden increase (HM), and RT-associated signature based on small deletion burden increase (RTscars). By deconvoluting RNA profiles into cell state fractions, we observed an increase of a proliferating stem-like (PSL) cell state in 50% of patients with a RTscars+ signature which was significantly higher than RTscars-/HM- patients (P=8e-04, Fisher’s exact). PSL cell state increase associated with worse overall survival outcomes (P=1.5e-03, log-rank). We observed a significant correlation between the expression change of E2F cell cycle regulator genes (R=0.91, P=6.7e-04, Pearson) and EZH2 (R=0.81, P=8.3e-03) with the increase in the PSL cell state, nominating the E2F/EZH2-pathway as regulator of the PSL cell state. Furthermore, the RTscars signature was associated with an increase in frameshift neoantigens and significantly higher neoantigen burden at recurrence (P=2.4e-02, Kruskal-Wallis). This was accompanied by a significantly higher post-treatment T-cell fraction in RTscars+ tumors (P=8.2e-04, Wilcox), suggesting an increased T-cell infiltration in these patients. Conclusion Our analyses revealed a longitudinal increase in the proliferating stem-like cell state associated with RT-resistance and nominates the cell cycle pathway as an actionable target. The RT-associated deletion signature (RTscars) correlated with increased frameshift-neoantigens and T-cell fractions at recurrence, suggesting a potential benefit of a combinatorial immune-targeted therapy in this specific patient population.

La surveillance de la santé consiste en l’utilisation systématique et continue de données sur la santé recueillies régulièrement en vue d’orienter les mesures de santé publique en temps opportun. Ce document décrit la création et l’essor des systèmes nationaux de surveillance au Canada et les répercussions de ces systèmes sur la prévention des maladies chroniques et des blessures. En 2008, les auteurs ont commencé à retracer l’historique des débuts de la surveillance nationale des maladies chroniques au Canada, en commençant à 1960, et ils ont poursuivi leur examen jusqu’en 2000. Une publication de 1967 a retracé l’historique de la création du Laboratoire d’hygiène de 1921 à 1967. Notre étude fait suite à cette publication et décrit l’historique de l’établissement de la surveillance nationale des maladies chroniques au Canada, à la fois avant et après la création du Laboratoire de lutte contre la maladie (LCDC).

Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100. mg enteric-coated aspirin will extend a composite primary endpoint termed 'disability-free life' including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65. years and above ('US minorities') and 70. years and above (non-'US minorities'). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100. mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.

This paper describes the rationale and basic design of the National Enhanced Cancer Surveillance System. The system is designed to facilitate timely, systematic evaluation of environment-cancer concerns and strengthen cancer surveillance in Canada. There are three key activities: (1) National community-level environmental quality database: The database, created by Health Canada, includes systematic, easily accessible, community-level information on air and water quality. Information includes a national inventory of municipal waste disposal sites, municipal drinking water data, air quality data, historic industrial location and productivity data. (2) Case-control surveillance: The Provincial Cancer Registries are collecting individual data from a large, Canada-wide, population-based series of newly-diagnosed cancer cases for 18 types of cancer and a population control group. Mailed questionnaires and telephone follow-up are used to gather data on residential and occupational histories, diet, physical activity and other risk factors for cancer. Data for over 20,000 cancer cases and 5000 controls have been assembled between 1994 and 1997. The cancer and population control data are being linked to the environmental database to facilitate systematic, community level, case-control assessment of cancer risk related to air and water quality. (3) Geographic surveillance network: Areas of high and/or unusual patterns of cancer incidence are being examined through temporal and spatial mapping, cluster analysis and risk factor evaluation. © 1998 John Wiley & Sons, Ltd.

Objectives To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment. Design Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials. Setting Women were recruited from 40 participating sites. Participants Cohort of 68 132 women followed through 2005 (parent study) and for an additional 5 years in the extension study. Main outcome measures Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the ‘no use’ category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications. Results Final models included 67 882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10 000 person-years among statin users and 5.0/10 000 person-years among non-users (p=0.11). The unadjusted risk of HS in statin users was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011. Conclusions This retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.

Aims In a large ethnically diverse nationwide sample of post-menopausal women we explored the relationship between fasting insulin levels, ethnicity, and a wide range of anthropometric, socio-economic, and lifestyle factors. Methods Subjects were post-menopausal women aged 50–79 years without diagnosed diabetes mellitus comprising a subsample (n = 3500) of the Women’s Health Initiative (WHI) Clinical Trial and Observational Study. In a crosssectional survey at baseline, we analysed the association between ethnicity and fasting insulin using analysis of covariance procedures and identified independent correlates of hyperinsulinaemia, defined by the 75th percentile cut point for each ethnic group. Results Fasting insulin levels were higher among African-American and Hispanic women than among non-Hispanic White or Asian women. These differences persisted after adjustment for age, educational attainment, total and central body obesity, adult weight change, family history of diabetes, smoking status, alcohol consumption, use of menopausal hormone therapy and physical activity. Higher levels of body mass index, waist–hip ratio, adult weight gain, and lower levels of total and moderate or strenuous recreational activity were independent correlates of fasting hyperinsulinaemia. Habitual walking was also inversely associated with fasting insulin. Conclusions In this cross-sectional analysis, fasting insulin levels were higher among African-American and Hispanic post-menopausal women as compared with non-Hispanic White and Asian women. In addition, obesity, adult weight gain, and low levels of moderate or strenuous physical activity were independently associated with hyperinsulinaemia.

During the marine sedimentation within the Togo coastal basin, the impact of input continental origin was very important despite their various nature and the sedimentary or diagenetic modifications demanded by active or passive receptive depositional environment. Sedimentary clays in the basin reflect climatic, tectonic and morphological evolution from the late Cretaceous through Tertiary: erosion, weathering, margins stabilisation, pedogenesis and basin subsidence. Key words: Clay mineral, sedimentation, coastal basin, Togo Maastrichtian, Palaeocene, Eocene, margin, subsidence, climate, trangression. Resume Tout au long de la sedimentation marine dans le bassin cotier du Togo, l\'impact des apports d\'origine continentale a toujours ete important, malgre leur nature variable et les modifications sedimentaires et diagenetiques imposees par le milieu recepteur actif ou passif. Les argiles sedimentaires du bassin refletent l\'evolution climatique, tectonique et morphologique du Cretace-Tertiare: erosion, alteration, stabilisation des marges, developpement des pedogeneses et subsidence du bassin. Mots cles: Argile minerale, sedimentation, bassin cotier, Togo Maastrichtien, Paleocene, Eocene, marge, subsidence, climat, transgression. (Af. J. of Science and Technology: 2002 3(2): 96-100)

Studies comparing ever smokers with never smokers have found little increase in breast cancer risk. However, the five published studies examining passive smoking and breast cancer have all suggested associations with both passive and active smoking, particularly premenopausal risk.We analyzed data collected through the Canadian National Enhanced Cancer Surveillance System, from 805 premenopausal and 1512 postmenopausal women with newly diagnosed (incident), histologically confirmed, primary breast cancer and 2438 population controls. The mailed questionnaire included questions on breast cancer risk factors and a lifetime residential and occupational history of exposure to passive smoking.Among premenopausal women who were never active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer odds ratio (OR) of 2.3 (95% confidence interval [CI] 1.2-4.6). Passive exposure showed a strong dose-response trend (test for trend p = 0.0007) with an OR of 2.9 (95% CI 1.3-6.6) for more than 35 years of passive residential and/or occupational exposure. When premenopausal women who had ever actively smoked were compared with women never regularly exposed to passive or active smoke, the adjusted OR for breast cancer was also 2.3 (95% CI 1.2-4.5). Among postmenopausal women who were never-active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer OR of 1.2 (95% CI 0.8-1.8) and an OR of 1.4 (95% CI 0.9-2.3) for the most highly exposed quartile of women. The adjusted OR for postmenopausal breast cancer risk for ever-active smokers compared with women never regularly exposed to passive or active smoke was 1.5 (95% CI 1.0-2.3). Statistically significant dose-response relationships were observed with increasing years of smoking, increasing pack-years and decreasing years since quitting. Women with 35 or more years of smoking had an adjusted OR of 1.7 (95% CI 1.1-2.7).Active and passive smoking may be associated with increased breast cancer risk, particularly premenopausal risk.

The relationship between alcohol, tobacco and coffee consumption and pancreatic cancer was investigated using population-based case-control data obtained from eight Canadian provinces. Our findings are based on analyses performed on 583 histologically confirmed pancreatic cancer cases and 4813 controls. Questionnaire data were obtained directly from 76% of the cases. Male subjects with 35 or more cigarette pack-years had an increased risk of developing pancreatic cancer relative to never smokers (OR= 1.46, 95% CI 1.00-2.14). Similarly, women reporting at least 23 cigarette pack-years of smoking had an odds ratio of 1.84 (95% CI 1.25-2.69). For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer. Coffee drinking was not related to pancreatic cancer. More work is needed to clarify the role of these and other potentially modifiable risk factors as a means to reduce the incidence of this disease for which treatment results remain disappointing.

Key to working with a consultant is knowing when to use one, how to select the right one and how to work effectively with one. Most of the ordinary business of an organization can be carried out using its own internal resources. When this is not the case, the external viewpoint of a consultant can be helpful. Determining if a consultant can add value is considered a first step in the consulting process. Ideally, the imaging manager is involved in this step. Finding the right consultant, much like other major decisions, can be done by talking with friends or colleagues, even using the internet and AHRA Listserv. Depending on the size and nature of the engagement, a request for proposal (RFP) may be appropriate to identify the amount of expertise needed for a particular situation. When a list of potential consultants is created, the next step is to call the references of each to find the closet fit. The next step is to develop a contract or letter of understanding with the selected consultant. When agreement is reached, the consultant may then request preliminary information to begin work on the project. A further decision is to determine whether the consultant will only make recommendations or will actually help with implementation. The project typically concludes with delivery of the consultant's written report. A facility should expect some major and important new thoughts to come from the consultant's work. An effective partnership with a consultant can go far in attaining a goal of increased levels of service and decreased costs.

The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure (BP) has been controlled for 1 year. However, discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events. The Trial of Nonpharmacologic Interventions in the Elderly (TONE) was a clinical trial of the efficacy of weight loss and/or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP145/85 mm Hg on 1 antihypertensive medication. Of 975 participants, 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications. Thirty-three events (stroke, transient ischemic attack, myocardial infarction, arrhythmia, congestive heart failure, angina, other) occurred between randomization and the onset of drug withdrawal (median time 3.6 months), 57 events occurred either during or after drug withdrawal (14.0 months), and 36 events occurred after resumption of antihypertensive therapy (15.9 months). Event rates per 100 person-years were 5.5, 5.5, and 6.8 for the 3 time periods (p=0.84) in the nonoverweight group and 7.2, 5.2, and 5.6 (p=0.08) in the overweight group. The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressureor = 150/90 mm Hg at withdrawal, providing that good BP control can be maintained with nonpharmacologic therapy.

Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation.To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension.Randomized controlled trial.A total of 975 [corrected] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication.Four academic health centers.The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention.Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months).The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups.Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates for tumor removal by surgery. Controls were selected among hospitalized patients with non-neoplastic and non-lung disease. The overall male lung-cancer risks associated with cigarette smoking were similar to those reported in other Chinese studies but quite low compared to risks in Western countries. However, the subjects in this study were relatively young (average age 53.2), had started to smoke on average at a relatively old age (21.3 years), and only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not strongly associated with any of the nutrients examined, when all cases were compared to all controls. However, the data were suggestive of differences in the relationship of diet to risk among smokers and non-smokers. Cautious interpretation is required because of the wide confidence intervals due to limited sample size. Among the smokers, only higher beta-carotene was associated with estimates suggesting a lowered risk. Among non-smokers, the evidence suggested that increased vegetable consumption might reduce risk, consumption of any fruit might reduce risk but beta-carotene was unrelated to risk. The differences observed in the relationship of diet to lung-cancer risk between Chinese smokers and non-smokers warrant further study.

To provide guidance in setting particle size specifications for poorly soluble drugs to minimize variability in absorption.A previously reported computer method was used to simulate the percent of dose absorbed as a function of solubility, absorption rate constant, dose, and particle size.The simulated percent of dose absorbed was tabulated over a realistic range of solubilities, absorption rate constants, and doses using drug particle sizes that might be typically found in a dosage form.The greatest effect of particle size on absorption was simulated for low dose- low solubility drugs. In general, the sensitivity of absorption to particle size decreased with increasing dose or solubility. At a solubility of 1 mg/mL, particle size had practically no effect on the percent of dose absorbed over the range of doses simulated (1-250 mg).

The dissolution rates of two lots of hydrocortisone (fine and coarse) were simulated using a computer program based on a Noyes-Whitney-type equation. Derivations of the equation were made to compare the accuracy of simulations using spherical and cylindrical particle geometry, with and without a time-dependent diffusion layer thickness. To approximate better the shape of the hydrocortisone particles, a shape factor was used to relate cylindrical length to radius. The most accurate simulations were obtained by assuming cylindrical geometry with and without a time-dependent diffusion layer thickness for the fine and coarse hydrocortisone, respectively. The program was also modified to simulate initial particle size distributions based on the log normal probability density function.

Residential fires are a leading cause of unintentional injury in the United States. We completed a cross-sectional study in an urban internal medicine clinic to describe the patients' risk factors for fire injury and internists' current methods for addressing this health problem. We used a physician self-report survey (n = 301), patient interviews (n = 300), and chart reviews (n = 300) in the evaluation. Among physicians returning the questionnaire (70% response rate), more than 85% demonstrated reasonable knowledge of injury as a major health problem and relatively positive attitudes toward incorporating injury prevention into clinical practice. However, 62% of physicians reported "never" and 23% only "seldom" counseling patients about smoke detectors. Among patients attending the clinic, only 63% reported having a smoke detector in their home. Factors associated with not having a smoke detector through multivariate logistic analysis were black race (odds ratio [OR] = 4.3, confidence interval [CI] = 1.7, 10.6) and patient report that physician did not counsel about smoke detectors (OR = 2.38, Cl = 1.15, 4.90). Age younger than 65 (OR = 1.7, Cl = .93, 2.9) and alcohol abuse (OR 1.5, Cl = .92, 2.5) were borderline in their statistical significance. Eighteen percent of the patients reported being counseled by their physician about smoke detectors, although no documentation appeared in any of the charts. In addition, those patients with risk factors for fire injury did not report being counseled more often than their lower risk counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

The Ah receptor regulates induction of cytochrome P450IA1 and mediates certain toxicities of polyhalogenated aromatics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been characterized previously in continuous cell lines, notably the mouse hepatoma line Hepa 1, the human squamous cell carcinoma line A431, and the human liver cell line Hep G2. The present work extends our knowledge of the Ah receptor in continuous human liver cell lines. Ah receptor can be detected in Mz-Hep-1, a hepatitis B virus-negative cell line derived from a Thorotrast-induced hepatocellular carcinoma. The mean concentration of Ah receptor in Mz-Hep-1 cells was 341 +/- 22 fmol/mg cytosol protein (mean +/- SEM, nine separate determinations). This is equivalent to approximately 30,000 sites per cell. The concentration of Ah receptor in Mz-Hep-1 cells is similar to that in Hepa 1 cells and approximately three times higher than that in Hep G2 cells. The Mz-Hep-1 Ah receptor sedimented in continuous sucrose gradients at approximately 9 S. Specificity of binding by [3H]TCDD was demonstrated by competitive binding of non-radiolabeled 2,3,7,8-tetrachlorodibenzofuran, 3-methylcholanthrene (MC), and dibenz[a,h]anthracene in 50-fold molar excess. Phenobarbital, which is not a substrate for P450IA1, did not compete with [3H]TCDD for binding to Mz-Hep-1 Ah receptor. Dexamethasone and estradiol also did not compete with [3H]TCDD for binding, suggesting non-identity of Ah receptor with glucocorticoid or estrogen receptor. In separate experiments, glucocorticoid receptor was identified in Mz-Hep-1 cells. By Scatchard plot analysis, the apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Mz-Hep-1 Ah receptor was estimated to be 4.4 nM, compared to 0.8 nM in Hepa 1 cells. By Woolf plot analysis the Kd was 5.4 nM, compared to 1.2 nM in Hepa 1 cells. The [3H]TCDD.Ah receptor complex extracted from nuclei of Mz-Hep-1 cells incubated with [3H]TCDD in culture at 37 degrees sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was detectable in Mz-Hep-1 cells after pretreatment with inducing chemicals. Mz-Hep-1 cells have the highest concentrations of Ah receptor in any continuous human liver cell line thus far investigated. The Mz-Hep-1 Ah receptor is similar physicochemically to that described in murine systems. AHH activity is inducible in Mz-Hep-1 cells.

Figure 1 Jud Wells in 2005 (photograph by Kenneth Johnson). At age 65, a time in life when most people are winding down and spending life recalling past accomplishment, Judson Wells started a new career after retiring as chemist and then executive at Dupont Chemical Company. This PhD in chemistry (Harvard undergraduate 1938 and PhD 1941) started working on lung cancer and secondhand smoke issues from his home in Kennett Square, Pennsylvania, as a volunteer for the American Lung Association. In retirement, Jud Wells became one of the most influential—if not widely recognised—epidemiologists in the world on the issue of secondhand smoke. He published the first comprehensive estimate of the deaths due to secondhand smoke in his landmark 1988 paper in Environment International .1 He was the first person to highlight the connection between passive smoking and heart disease. While very controversial at the time, the conclusion that secondhand smoke causes heart disease was a central new health conclusion in the 2006 Surgeon General’s report2 18 years later. Jud’s work on heart disease had a major effect—it demonstrated clearly that heart disease—not lung cancer—was the main source of premature death from passive smoking exposure. His 1988 paper estimated that passive smoking was causing 50 000 deaths per …

Niacin (nicotinic acid) is available in several forms, including crystalline preparations and various types of sustained-release preparations. Evidence exists that sustained-release niacin, with respect to both dosage and severity, is more hepatotoxic than crystalline niacin. Three patients who developed hepatitis during treatment with sustained-release niacin were rechallenged with equivalent or higher doses of crystalline niacin, with no evidence of recurring hepatocellular damage. Although the mechanism for niacin-induced hepatitis is unknown, these cases support previous observations that crystalline niacin may be less hepatotoxic than sustained-release preparations in certain patients.

Editor—Josefson reports on a study by Lydon-Rochelle et al that found that induction of labour was associated with increased risk of uterine rupture.1 Although the research isolated prostaglandins from other forms of induction, it failed to isolate those women induced specifically with oxytocic drugs and those who were not induced but were given augmentation. This more specific stratification could entirely change the risk levels and clinical implications for particular groups. The study found that induction of labour without prostaglandins increased the relative risk significantly (to 4.9). As this cohort presumably included women who had induction by artificial rupture of the membranes, medicated forms of induction within this “other” category could pose an even higher relative risk. Recent studies looking at augmentation have found it also to be associated with uterine rupture.2–5 For example, Zelop et al found that induction with oxytocin was associated with a 4.6-fold increase in uterine rupture, and augmentation with a 2.3-fold increase.4 Because it is reasonable to assume that a good portion of the “inductions without prostaglandins” in the study reported by Josefson involved oxytocics, oxytocin induction and augmentation may be implicated. By not clarifying which mothers were given augmentation the study lacks a clear cohort of mothers who had no intervention at all. Women who have had a previous caesarean section but neither induction nor augmentation could prove to be at lower risk of rupture than any of the groups isolated in the study. Isolating women who had no medicinal or mechanical stress could show that vaginal delivery for these women has a similar level of safety as the prescribed elective repeat caesarean.

Coupled-wave theory is developed in full generality for unrestricted grating and polarization geometries. The analysis applies to composite gratings modulated dielectrically, magnetically, and in absorptivity; and is also developed for gratings nonuniform with depth.

The phenomenon of image reconstruction from an absorptionless volume hologram is analyzed using coupled-wave diffraction theory. Reconstruction efficiency formulas are derived, which apply when the hologram intermodulation component is negligible and when no extraneous diffracted orders of significant amplitude are generated. Both transmission and reflection holograms are considered, and the analysis is developed for diffraction geometries in which polarization effects are appreciable.

A simple but accurate coupled-wave theory describing diffraction from a volume grating is developed, which applies to planar diffraction geometries with the electric field polarized normal to the plane of incidence. Modulation of the dielectric and the absorption properties of the medium are considered, and the analysis is developed for gratings nonuniform with depth and for composite (multiplexed) gratings. The theory is based axiomatically on Maxwell's equations, and no approximations or simplifying assumptions other than those requisite to the scalar wave formulation of the theory enter into the analysis (except that for computational applications, only a finite number of diffracted orders may be retained in the analysis).

(1934). NOTES ON NESTING BIRDS OF THE ORANGE FREE STATE. Ostrich: Vol. 5, No. 2, pp. 49-56.

An alternative formulation of coupled-wave theory adapted to numerical analyses is developed, using the method of invariant imbedding. Solutions of the coupled-wave equations are represented in terms of a reflectance matrix ϱ and a transmission matrix τ (rather than the transition matrix Φ of the more classical approach).