Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders

Alcohol use disorders (AUDs) are complex and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinical data provide evidence that nicotine administration increases alcohol intake and nonspecific nicotinic receptor antagonists reduce alcohol-mediated behaviors. As nicotine interacts specifically with the neuronal nicotinic acetylcholine receptor (nAChR) system, this suggests that nAChRs play an important role in the behavioral effects of alcohol. In this review, we discuss the importance of nAChRs for the treatment of AUDs and argue that the use of FDA approved nAChR ligands, such as varenicline and mecamylamine, approved as smoking cessation aids may prove to be valuable treatments for AUDs. We also address the importance of combining effective medications with behavioral therapy for the treatment of alcohol dependent individuals.

Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.

Data preprocessing for anomaly based network intrusion detection : a review

Data preprocessing is widely recognized as an important stage in anomaly detection. This paper reviews the data preprocessing techniques used by anomaly-based network intrusion detection systems (NIDS), concentrating on which aspects of the network traffic are analyzed, and what feature construction and selection methods have been used. Motivation for the paper comes from the large impact data preprocessing has on the accuracy and capability of anomaly-based NIDS. The review finds that many NIDS limit their view of network traffic to the TCP/IP packet headers. Time-based statistics can be derived from these headers to detect network scans, network worm behavior, and denial of service attacks. A number of other NIDS perform deeper inspection of request packets to detect attacks against network services and network applications. More recent approaches analyze full service responses to detect attacks targeting clients. The review covers a wide range of NIDS, highlighting which classes of attack are detectable by each of these approaches. Data preprocessing is found to predominantly rely on expert domain knowledge for identifying the most relevant parts of network traffic and for constructing the initial candidate set of traffic features. On the other hand, automated methods have been widely used for feature extraction to reduce data dimensionality, and feature selection to find the most relevant subset of features from this candidate set. The review shows a trend toward deeper packet inspection to construct more relevant features through targeted content parsing. These context sensitive features are required to detect current attacks.

Me and my body : the relevance of the difference for the distinction between withdrawing life support and euthanasia

In this paper I discuss David Shaw’s claim that the body of a terminally ill person can be conceived as a kind of life-support, akin to an artificial ventilator. I claim that this position rests upon an untenable dualism between the mind and the body. Given that dualism continues to be attractive to some thinkers, I attempt to diagnose the reasons why it continues to be attractive, as well as to demonstrate its incoherence, drawing on some recent work in the philosophy of psychology. I conclude that, if my criticisms are sound, Shaw’s attempt to deny the distinction between withdrawal and euthanasia fails.