Incommensurable worldviews? Is public use of complementary and alternative medicines incompatible with support for science and conventional medicine?

Proponents of controversial Complementary and Alternative Medicines, such as homeopathy, argue that these treatments can be used with great effect in addition to, and sometimes instead of, ?conventional? medicine. In doing so, they accept the idea that the scientific approach to the evaluation of treatment does not undermine use of and support for some of the more controversial CAM treatments. For those adhering to the scientific canon, however, such efficacy claims lack the requisite evidential basis from randomised controlled trials. It is not clear, however, whether such opposition characterises the views of the general public. In this paper we use data from the 2009 Wellcome Monitor survey to investigate public use of and beliefs about the efficacy of a prominent and controversial CAM within the United Kingdom, homeopathy. We proceed by using Latent Class Analysis to assess whether it is possible to identify a sub-group of the population who are at ease in combining support for science and conventional medicine with use of CAM treatments, and belief in the efficacy of homeopathy. Our results suggest that over 40% of the British public maintain positive evaluations of both homeopathy and conventional medicine simultaneously. Explanatory analyses reveal that simultaneous support for a controversial CAM treatment and conventional medicine is, in part, explained by a lack of scientific knowledge as well as concerns about the regulation of medical research

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells

Modeling Structure-Function Relationships in Synthetic DNA Sequences using Attribute Grammars

Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part. This concept provides a finer level of granularity than the traditional notion of the gene. However, a method of formally relating how a set of parts relates to a function has not yet emerged. Synthetic biology both demands such a formalism and provides an ideal setting for testing hypotheses about relationships between DNA sequences and phenotypes beyond the gene-centric methods used in genetics. Attribute grammars are used in computer science to translate the text of a program source code into the computational operations it represents. By associating attributes with parts, modifying the value of these attributes using rules that describe the structure of DNA sequences, and using a multi-pass compilation process, it is possible to translate DNA sequences into molecular interaction network models. These capabilities are illustrated by simple example grammars expressing how gene expression rates are dependent upon single or multiple parts. The translation process is validated by systematically generating, translating, and simulating the phenotype of all the sequences in the design space generated by a small library of genetic parts. Attribute grammars represent a flexible framework connecting parts with models of biological function. They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts. This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology

Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder

Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB).We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability