Search

Encouraging entrepreneurship is an effective way to empower women. While most nations have policies empowering women, are these policies effective in encouraging female entrepreneurship? Additionally, is there a gap between policy enactment and enforcement that hinders entrepreneurship? In this short article, we start a conversation by examining cross-country differences in female entrepreneurship and relating them to existing social, educational, and workplace policies. Further, we suggest a novel measure of enforcement that effectively captures the divergence between stated policies and successful reduction of discriminatory practices on the ground, providing us a tool to isolate cheap talk from effective policy intervention.

As the critical dimensions (CDs) of etch profiles continue to decrease, precise control of plasma etch processing becomes increasingly important. Achieving this control requires optimizing etch recipes, which is time consuming and expensive as an extensive amount of experiments must be performed. Here we present a method for the prediction of process windows to achieve target CDs for high aspect ratio trenches using model-based experimental design. A reduced-order model of the physics and chemistry of the etch is used to identify the best experiments to perform to calibrate the model. The model is then used to efficiently explore the process parameter space to identify the largest ranges of process parameters that achieve desired ranges of CDs. The methodology is practically demonstrated on a three-step trench etch through three layers of material consisting of spin-on-glass, spin-on-carbon and silicon. It is found that this physics-model based method requires less than half as many experiments to identify the optimal etch recipe than full-factorial design of experiments.

We present a model-based experimental design methodology for accelerating 3D etch optimization with demonstration on 3D NAND structures. The design and optimization of etch recipes for such 3D structures face significant challenges requiring costly and time-consuming experiments in order to achieve the required tolerances. 3D NAND memory devices additionally require accurate nanofabrication of high aspect ratio trenches and isolation slits, which are challenging to manufacture reliably within specifications. Our model efficiently captures the relevant physical and chemical processes, which allows them to be calibrated using a limited number of experimental samples and can reproduce realistic 3D etch of multilayer materials, including bowing, necking, and tapering. Since our GPU-powered simulations run in a matter of minutes, the relevant process parameter space can be explored extensively in a short amount of time. The calibrated physics-based model can be used to train adaptive machine-learning-based heuristics which enable near-instant queries, for example for data visualization and analytics. With this approach, we show a rapid methodology for locating optimal windows in the process parameter space for etching 3D structures. Optimality metrics under consideration include both conformances to specified tolerances as well as robustness against process parameter variations. These techniques can reduce cost and time to market for complex multi-layer three-dimensional device designs and improve semiconductor device yields.

Globally, there is a growing demand for biocatalysts because of the associated efficacy and efficiency. The applications of enzymes in food, paper, pulp, textile, and chemical industries have prompted enzyme exploration. Microbes, being the natural reservoirs of enzymes, have gained researchers’ attention, and the quest for microbial enzymes has increased in past years. This review provides insights about metagenomics techniques and their applicability in obtaining microbial-origin enzymes from diverse environmental samples besides highlighting their importance. The metagenomic approach has emerged as a promising way towards replacing conventional microbial techniques with culture-independent methods involving direct isolation of DNA environmental samples. There are two primary methodologies, i.e., functional-based and sequence-based, to identify and characterize industrially valuable biocatalysts from the environmental microcosms. Many of the obtained enzymes are successfully used in diverse food, cosmetics, and pharmaceutical industries. However, there are some complications associated with it that can be minimized only by further investigations. The paper focuses on the advancement of metagenomics for bioprospecting to stress on its significance in microbial characterization and exploration. This will also ensure the in-depth analysis of several unexplored and unknown microbial communities and/or members from complex niches.

Online medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: 1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica’s Dollars for Docs (PDD) and 2) quantifies CoIs among authors of a publically available point of care clinical support website. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payment were determined for 2013-2015. The subset of highly compensated authors that also reported “Nothing to disclose” were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R2 ≥ 0.998) and payment number (R2 ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson’s Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting “Nothing to disclose” received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.

Summary This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

In municipal waste effluent treatment, ammonia removal by an inorganic cation exchanger is practiced in a few communities. However, cost is a major consideration by municipalities when it comes to applying new technologies. Some parts of the US, Southern California, for example, long faced with a deficit of good quality fresh water, have available a potential source in its once-used wastewater. An efficient, economical, and reliable demineralization process which can be adapted to the special problems encountered in wastewater treatment would eliminate one of the obstacles in the utilization of several million acre feet of wastewater being discharged annually to the oceans. Continuous countercurrent ion exchange has been successfully used for several pollution control applications. However, ion exchange also increases the total amount of solids in the regenerant waste streams. But for many applications and with the proper choice of regenerant chemicals, the concentrated waste stream can be recovered as a by-product.

P21 Activated Kinase 1 (Pak1), an oncogenic serine/threonine kinase, is known to have a significant role in the regulation of cytoskeleton and cellular morphology. Runx3 was initially known for its role in tumor suppressor function, but recent studies have reported the oncogenic role of Runx3 in various cancers. However, the mechanism that controls the paradoxical functions of Runx3 still remains unclear. In this study, we show that Runx3 is a physiologically interacting substrate of Pak1. We identified the site of phosphorylation in Runx3 as Threonine 209 by mass spectrometry analysis and site-directed mutagenesis, and further confirmed the same with a site-specific antibody. Results from our functional studies showed that Threonine 209 phosphorylation in Runx3 alters its subcellular localization by protein mislocalization from the nucleus to the cytoplasm and subsequently converses its biological functions. This was further supported by in vivo tumor xenograft studies in nude mouse models which clearly demonstrated that PANC-28 cells transfected with the Runx3-T209E clone showed high tumorigenic potential as compared with other clones. Our results from clinical samples also suggest that Threonine 209 phosphorylation by Pak1 could be a potential therapeutic target and of great clinical relevance with implications for Runx3 inactivation in cancer cells where Runx3 is known to be oncogenic. The findings presented in this study provide evidence of Runx3-Threonine 209 phosphorylation as a molecular switch in dictating the tissue-specific dualistic functions of Runx3 for the first time.

A potent sarcoma virus was isolated after in vivo passage of a tumor arising spontaneously in a New Zealand White × New Zealand Black (B/ W) F1 hybrid mouse. Inoculation of the virus into mice, rats, hamsters, and Mastomys resulted in the rapid development of tumors at the sites of inoculation. The tumors induced in mice were sarcomas consisting of spindle cells and many inflammatory cells. Most tumors had a prominent angiomatous component. Tumor regressions occurred in some mice, while other tumors grew progressively, metastasized, and resulted in death. B/ W mice developed splenomegaly 4-6 weeks after virus inoculation. The normal architecture of their spleens was completely destroyed and replaced by angiomatous tissue, fibrosis, and inflammatory changes. Virus-induced tumors in hamsters consisted of undifferentiated polygonal cells. Virus-induced tumors of rats and Mastomys consisted of thin-walled blood vessels heavily infiltrated with polymorphonuclear leukocytes. Primary virus-induced tumors in hamsters, rats, and Mastomys did not regress, but some transplanted hamster tumors regressed. Electron microscopy of virus-induced and transplanted tumors revealed numerous type-C virus particles morphologically similar to the murine leukemia-sarcoma viruses. Tumor homogenates contained the group-specific (gs) antigen of the murine leukemia-sarcoma viruses.

Summary Ataxia-Telangiectasia (A-T) is a genetic condition leading to neurological defects and immune deficiency. The nature of the immune deficiency is highly variable, and in some cases causes significant morbidity and mortality due to recurrent sinopulmonary infections. Although the neurological defects in A-T are progressive, the natural history of the immune deficiency in A-T has not been evaluated formally. In this study we analyse the clinical history and immunological data in 44 patients with A-T who attended the National Ataxia-Telangiectasia clinic in Nottingham between 2001 and 2011. Using patient medical records and Nottingham University Hospitals (NUH) National Health Service Trust medical IT systems, data regarding clinical history, use of immunoglobulin replacement therapy, total immunoglobulin levels, specific antibody levels and lymphocyte subset counts were obtained. T cell receptor spectratyping results in some patients were already available and, where possible, repeat blood samples were collected for analysis. This study shows that subtle quantitative changes in certain immunological parameters such as lymphocyte subset counts may occur in patients with A-T over time. However, in general, for the majority of patients the severity of immune deficiency (both clinically and in terms of immunological blood markers) does not seem to deteriorate significantly with time. This finding serves to inform the long-term management of this cohort of patients because, if recurrent respiratory tract infections present later in life, then other contributory factors (e.g. cough/swallowing difficulties, underlying lung disease) should be investigated aggressively. Our findings also offer some form of reassurance for parents of children with A-T, which is otherwise a progressively severely debilitating condition.

Summary India has a rich diversity of cattle, buffalo, sheep and goat breeds which are not only important to the people of India, but have contributed significantly to livestock programmes in many other tropical and sub-tropical climatic areas of the world. Most important is the fact that our domestic animal genetic resources (AGR) are under threat. This paper highlights the main AGR of India; the threat to biodiversity and the efforts made for conserving and improving indigenous livestock breeds. Resumen La India posee una buena diversidad de razas bovinas, bœfalos, ovinos y caprinos que no sUlo son importantes para la poblaciUn india, si no que han participado de forma significante en los programas ganaderos de muchas otras zonas climAEticas tropicales y sub tropicales en el mundo. Un hecho importante es que nuestros recursos genOticos animales (AGR) se encuentran en peligro. Este artIculo subraya los principales AGR en la India; el peligro para la biodiversidad y los esfuerzos realizados para conservar y mejorar las razas ganaderas indIgenas.

1. The involvement of protein kinase C (PKC) in constriction of small bronchioles has never been investigated. In this study we have examined the effects of the specific PKC inhibitors Ro31-8220 and Ro31-7549 and the non-specific inhibitor H7 on carbachol-, 5-hydroxytryptamine (5-HT)- and 4 beta-phorbol dibutyrate (4 beta-PDBu)-induced contractions in large and small bronchioles. 2. The study was performed on isolated bronchioles of the rat with internal diameters of 574 microns +/- 11 (small, n = 128), and 1475 microns +/- 32 (large, n = 93), using a Mulvaney-Halpen small vessel myograph. 3. In these preparations 4 beta-PDBu had no effect if added on its own. However, after precontracting with 30 mM K+, 0.5 microM 4 beta-PDBu caused a contractile response of 110.4 +/- 7.0% TK (TK = maximum response to 75 mM K+ in small and 69.3 +/- 6.5% TK in large bronchioles. Ro31-8220, Ro31-7549 and H7 all showed concentration-dependent inhibition of this response. 4. In small bronchioles 10 microM Ro31-8220 shifted both the carbachol and 5-HT concentration-response curves to the right, and reduced the maximum response. In contrast, 10 microM Ro31-8220 had no significant effect on the EC50 to carbachol of larger bronchioles, although the maximum response was reduced, and had no significant effect on the 5-HT concentration-response curve. 200 microM H7 shifted the carbachol concentration--response curve to the right as well as reducing the maximal response in both small and large bronchioles. 5 Large bronchioles exhibited a greater rate of decay of carbachol-induced contraction than did small bronchioles. Pretreatment with Ro31-8220 accelerated the rate of decay.6 Pretreatment with 10 JM Ro3l-8220 caused a small reduction in the response to 75 mM K+ in both small and large bronchioles (small: to 87.8 +/- 3.0% TK; large: to 94.1 +/- 0.8% TK). H7 at 200 JM caused a much larger reduction in both preparations (small: to 75.1 +/- 3.0% TK); large: to 82.7 +/- 0.6% TK).7 Small bronchioles were more sensitive than larger bronchioles to agonists and phorbol ester. The protein kinase inhibitor Ro31-8220 could reduce agonist-induced constriction in small and large bronchioles,as well as reducing or abolishing phorbol ester-induced contractions. Small bronchioles were more sensitive than large bronchioles to Ro31-8220. These results suggest that there is a significant PKC involvement in constriction of bronchioles to carbachol and 5-HT, and that the proportion of the contractile response that can be attributed to PKC is greater in smaller than larger bronchioles.

1. The interaction between inositol 1,4,5-trisphosphate (InsP3) and guanosine 5'-O-(3-thio triphosphate) (GTP gamma S) releasable calcium (Ca2+) pools was examined using 45Ca effluxes in permeabilized cultured airway smooth muscle cells from rabbit trachea. 2. Addition of InsP3 or GTP gamma S caused a concentration-dependent release of intracellular Ca2+. The release of Ca2+ by InsP3 was much greater than with GTP gamma S. Pretreatment with maximally effective InsP3 (10 microM) abolished the GTP gamma S-induced Ca2+ release, whereas pretreatment with 100 microM GTP gamma S reduced the InsP3-induced Ca2+ release by 25%. 3. Ryanodine (100 microM), also gave a large release of intracellular Ca2+. After pretreatment with 100 microM ryanodine, GTP gamma S did not induce Ca2+ release, and InsP3-induced Ca2+ release was reduced by 76%. 4. Caffeine (50 mM), produced a slow release of intracellular Ca2+. Pre-exposure to 50 mM caffeine had no effect on the GTP gamma S-induced Ca2+ release but reduced the InsP3 releasable Ca2+ by 58%. 5. Pretreatment with ryanodine abolished the caffeine-induced Ca2+ release, and addition of caffeine before ryanodine reduced the ryanodine-induced Ca2+ release by 64.4%. 6. These results suggest that there are at least three pools of Ca2+ present within airway smooth muscle cells. The largest pool is released by InsP3 or ryanodine, another is released either by a high concentration of InsP3 or on application of GTP gamma S, and the third by InsP3 alone. Ca2+ may be able to move from the GTP gamma S-sensitive pool into the InsP3- and ryanodine-sensitive pool when this becomes depleted. In contrast, the opposite movement of Ca2 + cannot occur.

It is now agreed that the prognosis of seizure disorder due to solitary cysticercus granuloma (SCG) is generally good. However, the choice antiepileptic drugs (AEDs) remain empirical, with no comparative trials of different AEDs being available.To determine the safety and efficacy (measured by the incidence of 'treatment failure') of clobazam in comparison to standard treatment with phenytoin-sodium for prevention of seizures in persons with solitary cysticercus granulomas (SCGs).This pilot study was conducted in a neurology department of a medical college hospital in the form of a prospective, randomized, open-labeled trial.Forty-eight patients with seizures due to SCG were randomized in an open-labeled trial to either, clobazam (1 mg/kg oral loading followed by 0.5 mg/kg/d) (n=21) or phenytoin (15 mg/kg, oral loading in 3 divided doses over 24 h, followed by 5 mg/kg/d) (n=27). They were followed over 6 months with the primary outcome measure being treatment failure (either discontinuation or modification of AEDs) due to either adverse effects or breakthrough seizures.Treatment failures were noted to be significantly less common (P =0.03) in the clobazam-treated group (n=1; 4.7%) than in phenytoin-treated group (n=9; 33.3%). These included one patient (4.7%) in the clobazam-group who had breakthrough seizures and 3 (11.1%) who had breakthrough seizures and 6 (22.2%) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation.Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG.

The role of protein tyrosine kinases (PTK) in modulating contractility has not been investigated in airway smooth muscle (ASM). We have examined the effects of the PTK inhibitors ST638, genistein, and tyrphostin A47 on contractions induced by carbachol, serotonin, ionomycin, and 75 mM KCl in isolated bronchioles of the rat with internal diameters of 614 +/- 16 microm (small, n = 143), and 1,433 +/- 39 microm (large, n = 57). ST638 caused a dose-dependent decrease in the maximum response to carbachol, and shifted the carbachol concentration-response curve to the right. This effect was greater in small bronchioles. Tyrphostin A47 (100 microM) and genistein (74 microM) had a similar effect to ST638. ST638 caused a concentration-dependent relaxation (EC50 approximately 7.2 microM) in bronchioles precontracted with 0.5 microM carbachol, and was maximally effective at 50 microM when tone was reduced by 82.5 +/- 3.8% in small bronchioles, and 57.2 +/- 2.8% in large bronchioles. ST638 also reduced the maximal response to serotonin, and caused a large shift to the right of the serotonin concentration-response curve. Pretreatment with ST638 (50 microM) reduced the response to 75 mM KCl in both small and large bronchioles in the presence of atropine (small: by 88.9 +/- 5.6%, n = 11; large: by 90.1 +/- 4.4%, n = 11). Tyrphostin A47 (100 microM) had a similar effect (91%). ST638 (50 microM) and tyrphostin A47 (100 microM) substantially relaxed small bronchioles contracted with 1.5 microM ionomycin (ST638: by 86.7 +/- 1.8%, n = 6; tyrphostin: by 89.3 +/- 1.7%, n = 5). We have therefore demonstrated that PTK inhibitors can suppress contraction induced by a number of different mechanisms in ASM. These results suggest that PTK signaling pathways are not only important for proliferation of ASM, but also fon contractile function.

The effects of BRL 38227 and glibenclamide on intracellular calcium stores were investigated in permeabilized cultured airway smooth muscle cells of the rabbit using 45Ca effluxes. BRL 38227 (10 microM) reduced loading of the inositol 1,4,5-trisphosphate (InsP3)-sensitive intracellular store by 26.5% +/- 1.0; this effect was antagonized by 1 microM glibenclamide. BRL 38227 itself did not release calcium and had no effect on guanosine 5'-0-(3-thiotriphosphate)-induced calcium release. Glibenclamide (greater than or equal to 5 microM) also reduced calcium loading of the intracellular store, and enhanced calcium release. These results suggest that BRL 38227 has a direct effect on intracellular calcium handling.

Synthetic glycolipids prepared by esterification of various sugars and sorbitol, and containing various numbers of saturated or unsaturated fatty acid residues as well as bacterial lipid A and lipopolysaccharide, were tested for mitogenicity of splenic cells of Fischer rats and Swiss mice and for the augmentation of humoral immune response against sheep red blood cells in these species. Subsequently a few of the humoral immune-response-enhancing glycolipids were compared with non-enhancers in their anti-tumour activity against 13762 rat mammary carcinoma in inbred Fischer 344 rats and Ehrlich tumour in Swiss mice. They were given systemically after tumour inoculation and intratumourally in squalene and Tween emulsion after intradermal MAC tumour development. It was observed that certain structural characteristics in glycolipids with respect to the type of sugar, the type and number of fatty-acid residues were needed for their adjuvant action of the humoral arm of the immune response. Although humoral immune-response enhancers were somewhat superior to non-enhancers in their anti-tumour activity, the correlation coefficient demonstrated a lack of significant concordance. It is concluded that glycolipids selected for their ability to augment humoral immune responses against standard antigens need not be suspect as tumour-enhancers on the grounds that they would elicit blocking antibodies in vivo against tumour-associated antigens.

Streptomyces griseoviridus produces in addition to etamycin several related compounds which can be separated by partition chromatography. One of these has been characterized by amino acid analysis and mass spectrometry and shown to have the same structure as etamycin except for replacement of the hydroxyproline residue by proline. Evidence was obtained for additional congeners similarly related to etamycin by amino acid exchange. The relative proportions of such congeners produced by S. griseoviridus depends upon the medium in which the culture is grown. Certain amino acids support good yields of the metabolites and the culture appears to be steered towards the synthesis of congeners containing such amino acids.

The effectivenss of maltose tetrapalmitate (MTP) as an antitumour immune adjuvant was verified by its comparison with other known immunopotentiators, namely BCG, Corynebacterium parvum, levamisole and pyran copolymer. Copenhagen x Fisher 344/CRBL F1 hybrid male rats inoculated s.c. with the Dunning R3327A prostatic adenocarcinoma were used as the test system. All animals treated with immunoadjuvants showed a delay in tumour appearance and inhibition of early tumour growth. MTP was found to be the most effective, followed by levamisole, BCG, pyran copolymer and C. parvum in order of decreasing efficacy. Intratumoral treatment of small or large s.c. tumours with BCG, MTP and C. parvum was ineffective in our cases. However, this treatment was effective with MTP and BCG if they were used against a differentiated form of R3327 tumour. MTP and levamisole were found to be equally effective when given orally in drinking water. Experiments involving surgical excision of tumours followed by MTP therapy in two s.c. implanted animal tumour models (viz. a poorly immunogenic ascites mammary carcinoma 13762 in Fisher 344/CRBL rats, and an SV40 virus-induced sarcoma of low immunogenicity in Syrian hamster) showed beneficial effects of MTP on local tumour recurrence and tumour growth. Pre- and postoperative MTP treatment was at least as effective as postoperative MTP treatment alone.

An established line of human breast carcinoma, MCF-7, when cultured within the artificial capillary system, formed solid masses of tissue. Acinar and ductular patterns developed, having the ultrastructural appearance of breast tissue that responds to exogenous hormones.

High-temperature passage (40.5°C) increased the incidence of flat variants obtained from Kirsten sarcoma virus transformed BALB/3T3 non-producer cells from less than 0.1% to 4%. The flat variants had growth properties similar to those of the BALB/3T3 line. The variant lines did not release detectable type C virus, but some contained intracisternal type-A particles. Super-infection of the variants with murine leukemia virus (MuLV) resulted in retransformation and release of sarcoma virus. Some of the variant lines may be suitable indicator cells for the assay of MuLV. Modal chromosome numbers of the variant lines were considerably higher than those of their progenitor cell line. Proprietes de Certains Mutants Morphologiques de Cellules Non Productrices Transformees par le Virus du Sarcome Murin Qui Ont Ete Isolees Apres Passage A Haute Temperature Un passage α haute temperature (40.5°C) a fait s'elever de moins de 0.1% α 4% l'incidence de certains mutants obtenus α partir de cellules BALB/3T3 non productrices transformees par le virus du sarcome de Kirsten. Ces mutants ont des proprietes de croissance analogues α celles de la lignee BALB/3T3. Les lignees de mutants n'ont pas libere de virus de type C en quantite decelable, mais certaines contenaient des particules intracisternales de type A. La surinfection des mutants avec le virus de la leucemie murine (MuLV) a entraǐne une retransformation et une liberation de virus du sarcome. Certaines lignees de mutants se prětent particulierement bien au dosage du MuLV. Le nombre modal de chromosomes etait notablement plus eleve dans les lignees de mutants que dans la lignee mere.

OBJECTIVE-To assess the risk of cardiorespiratory symptoms and mortality in non-smokers who were passively exposed to environmental smoke. DESIGN--Prospective study of cohort from general population first screened between 1972 and 1976 and followed up for an average of 11.5 years, with linkage of data from participants in the same household. SETTING--Renfrew and Paisely, adjacent burghs in urban west Scotland. SUBJECTS--15,399 Men and women (80% of all those aged 45-64 resident in Renfrew or Paisley) comprised the original cohort; 7997 attended for multiphasic screening with a cohabitee. Passive smoking and control groups were defined on the basis of a lifelong non-smoking index case and whether the cohabitee had ever smoked or never smoked. MAIN OUTCOME MEASURE--Cardiorespiratory signs and symptoms and mortality. RESULTS--Each of the cardiorespiratory symptoms examined produced relative risks greater than 1.0 (though none were significant) for passive smokers compared with controls. Adjusted forced expiratory volume in one second was significantly lower in passive smokers than controls. All cause mortality was higher in passive smokers than controls (rate ratio 1.27 (95% confidence interval 0.95 to 1.70)), as were all causes of death related to smoking (rate ratio 1.30 (0.91 to 1.85] and mortality from lung cancer (rate ratio 2.41 (0.45 to 12.83)) and ischaemic heart disease (rate ratio 2.01 (1.21 to 3.35)). When passive smokers were divided into high and low exposure groups on the basis of the amount smoked by their cohabitees those highly exposed had higher rates of symptoms and death. CONCLUSION--Exposure to environmental tobacco smoke cannot be regarded as a safe involuntary habit.