Macrophage-mediated clearance of cells undergoing caspase-3-independent death

Little is known of the functions of caspases in mediating the surface changes required for phagocytosis of dying cells. Here we investigate the role played by the effector caspase, caspase-3 in this process using the caspase-3-defective MCF-7 breast carcinoma line and derived caspase-3-expressing transfectants. Our results indicate that, while certain typical features of apoptosis induced by etoposide – namely classical morphological changes and the ability to degrade DNA into oligonucleosomal fragments – are caspase-3-dependent, loss of cell adhesion to plastic and the capacity to interact with, and to be phagocytosed by, human monocyte-derived macrophages – both by CD14-dependent and CD14-independent mechanisms – do not require caspase-3. Furthermore, both etoposide-induced caspase-3-positive and -negative MCF-7 cells suppressed proinflammatory cytokine release by macrophages. These results demonstrate directly that cell surface changes that are sufficient for anti-inflammatory clearance by human macrophages can be regulated independently of stereotypical features of the apoptosis programme that require caspase-3.

Cyberstalking:a new challenge for criminal law

Cyberstalking has recently emerged as a new and growing problem and is an area that will probably receive a higher profile within criminal law as more cases reach court (see Griffiths, 1999; Griffiths, Rogers and Sparrow, 1998; Bojic and McFarlane, 2002a; 2002b). For the purposes of this article we define cyberstalking as the use of information and communications technology (in particular the Internet) in order to harass individuals. Such harassment may include actions such as the transmission of offensive e-mail messages, identity theft and damage to data or equipment. Whilst a more comprehensive definition has been presented elsewhere (Bocij and McFarlane, 2002), it is hoped that the definition here is sufficient for those unfamiliar with this field. The stereotypical stalker conjures up images of someone harassing a victim who is the object of their affection. However, not all stalking incidents are motivated by unrequited love. Stalking can also be motivated by hate, a need for revenge, a need for power and/or racism. Similarly, cyberstalking can involve acts that begin with the issuing of threats and end in physical assault. We also make distinctions between conventional stalking and cyberstalking. Whilst some may view cyberstalking as an extension of conventional stalking, we believe cyberstalking should be regarded as an entirely new form of deviant behaviour. It is not surprising that cyberstalking is sometimes thought of as a trivial problem. A number of writers and researchers have suggested that cyberstalking and associated activities are of little genuine concern. Koch (2000), for example, goes as far as accusing those interested in cyberstalking as promoting hysteria over a problem that may be minuscule or even imaginary. The impression gained is that cyberstalking represents a relatively small problem where victims seldom suffer any real harm. Whilst there are no genuinely reliable statistics that can be used to determine how common cyberstalking incidents are, a great deal of evidence is available to show that cyberstalking is a significant and growing problem (Griffiths et al, 1998). For instance, CyberAngels (a well-known Internet safety organization) receives some 500 complaints of cyberstalking each day, of which up to 100 represent legitimate cases (Dean, 2000). Another Internet safety organization (Working to Halt Online Abuse) reports receiving an average of 100 cases per week (WHOA, 2001). To highlight the types of cyberstalking behaviours that take place and some of the major issues facing criminal law, we briefly examine four high profile cases of cyberstalking (adapted from Bocij and MacFarlane, 2002b).

Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis

Funding • The pooled data coordination team (PBoffetta, MH, YCAL) were supported by National Cancer Institute grant R03CA113157 and by National Institute of Dental and Craniofacial Research grant R03DE016611 • The Milan study (CLV) was supported by the Italian Association for Research on Cancer (Grant no. 10068). • The Aviano study (LDM) was supported by a grant from the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research • The Italy Multicenter study (DS) was supported by the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. • The Study from Switzerland (FL) was supported by the Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]. • The central Europe study (PBoffetta, PBrenan, EF, JL, DM, PR, OS, NS-D) was supported by the World Cancer Research Fund and the European Commission INCOCOPERNICUS Program [Contract No. IC15- CT98-0332] • The New York multicentre study (JM) was supported by a grant from National Institute of Health [P01CA068384 K07CA104231]. • The study from the Fred Hutchison Cancer Research Center from Seattle (CC, SMS) was supported by a National Institute of Health grant [R01CA048996, R01DE012609]. • The Iowa study (ES) was supported by National Instituteof Health [NIDCR R01DE011979, NIDCR R01DE013110, FIRCA TW001500] and Veterans Affairs Merit Review Funds. • The North Carolina studies (AFO) were supported by National Institute of Health [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]. • The Tampa study (PLazarus, JM) was supported by National Institute of Health grants [P01CA068384, K07CA104231, R01DE013158] • The Los Angeles study (Z-F Z, HM) was supported by grants from National Institute of Health [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. • The Houston study (EMS, GL) was supported by a grant from National Institute of Health [R01ES011740, R01CA100264]. • The Puerto Rico study (RBH, MPP) was supported by a grant from National Institutes of Health (NCI) US and NIDCR intramural programs. • The Latin America study (PBoffetta, PBrenan, MV, LF, MPC, AM, AWD, SK, VW-F) was supported by Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a‘ Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222] • The IARC multicentre study (SF, RH, XC) was supported by Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/ 0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. • The Boston study (KKelsey, MMcC) was supported by a grant from National Institute of Health [R01CA078609, R01CA100679]. • The Rome study (SB, GC) was supported by AIRC (Italian Agency for Research on Cancer). • The US multicentre study (BW) was supported by The Intramural Program of the National Cancer Institute, National Institute of Health, United States. • The Sao Paolo study (V W-F) was supported by Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP No 10/51168-0) • The MSKCC study (SS, G-P Y) was supported by a grant from National Institute of Health [R01CA051845]. • The Seattle-Leo stud (FV) was supported by a grant from National Institute of Health [R01CA030022] • The western Europe Study (PBoffetta, IH, WA, PLagiou, DS, LS, FM, CH, KKjaerheim, DC, TMc, PT, AA, AZ) was supported by European Community (5th Frame work Programme) grant no QLK1-CT-2001- 00182. • The Germany Heidelberg study (HR) was supported by the grant No. 01GB9702/3 from the German Ministry of Education and Research.

Designing for Safety : Implications of a Fifteen Year Review of Swallowed and Aspirated Dentures

Peer reviewed

Determining Pathways to Improvements in Fatigue in Rheumatoid Arthritis : Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Funded by: The Institute of Applied Health Sciences, University of Aberdeen The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis British Society for Rheumatology to the University of Manchester Schering-Plough Wyeth Laboratories Abbott Laboratories Amgen

Determining Pathways to Improvements in Fatigue in Rheumatoid Arthritis : Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Funded by: The Institute of Applied Health Sciences, University of Aberdeen The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis British Society for Rheumatology to the University of Manchester Schering-Plough Wyeth Laboratories Abbott Laboratories Amgen

Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer

Peer reviewed

The Longitudinal Course of Fatigue in Rheumatoid Arthritis : Results from the Norfolk Arthritis Register

Acknowledgment: The authors would like to thank the University of Manchester for access to the Norfolk Arthritis Register data and Professor Deborah Symmons for comments on an earlier draft of the manuscript. K.L.D. is funded by a studentship from the Institute of Applied Health Sciences, University of Aberdeen.

The changes in pain which mediate Reductions in fatigue likely reflect central not peripheral mechanisms : Results from the BSRBR-RA

Peer reviewed

Predicting functional disability : One year results from the Scottish Early Rheumatoid Arthritis Inception Cohort

Peer reviewed

Differences in the prevalence of ankylosing spondylitis in primary and secondary care : only one-third of patients are managed in rheumatology

Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: G.T.J. and G.J.M. have received research funding from Pfizer and AbbVie. L.E.D. conducted the analysis while funded by an Medical Research Council PhD studentship

EULAR revised recommendations for the management of fibromyalgia

Funding The project was funded by EULAR.

The Role of the Sentence-Tokened

Peer reviewed

Is alcohol consumption related to likelihood of reporting chronic widespread pain in people with stable consumption? : Results from UK Biobank

Acknowledgements This research has been conducted using the UK Biobank resource, and was funded by the University of Aberdeen. The authors have no conflicts of interest to declare.