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Adolescents with autism spectrum disorder (ASD) are at a heightened risk for obesity. Family-level measures of nutrition and physical activity may help explain factors contributing to disproportionate rates of weight gain. Twenty adolescents with ASD participated in baseline testing for a study to assess the feasibility of remotely-delivered yoga. Parents completed the Family Nutrition and Physical Activity (FNPA) survey and anthropometrics and physical activity were assessed in the adolescents. A median split was applied to the FNPA score to create high and low obesogenic environments and nonparametric O'Brien's multiple endpoint tests were used to evaluate the differences. Between-group differences were found in anthropometrics (p = 0.01) but not physical activity (p = 0.72). Implications for a multifaceted family-based approach to obesity prevention are discussed.

Advances in sensor technology and machine learning as well as the widespread use of smartphones are shifting the focus of healthcare. Emerging paradigms such as cyber-physical systems (CPSs) make possible the transition from reactive to preventive care. CPSs can be implemented to achieve effective mobile health solutions and to provide sophisticated new mechanisms to monitor an individual’s state in real-time via the use of sensors and mobile devices. Despite the significant potential impact of such systems, their implementation poses a range of complex technical challenges. This article surveys the state-of-the-art in implementations of CPSs for real-time personalized interventions. A general three layer architecture which can be used to consider current implementations is first presented along with a description of its main components. We also propose a three level taxonomy in accordance with the system capabilities. Then, the principal technical challenges, human-machine interaction challenges and future directions are discussed. Fifteen of the state-of-the-art implementations are qualitatively evaluated in terms of sensor capabilities, just-in-time reaction, interruptibility, and adherence, among other characteristics. By reviewing the state-of-the-art of the systems that have been built to-date, the focus of the review is to summarize current technical challenges and future opportunities for both future CPS implementers and behavioral scientists designing CPS for personalized interventions.

Crowdsensing refers to an approach for collecting of data from a large number of smart devices and sensors carried by many individuals and has been employed for numerous applications, which include pollution monitoring, traffic monitoring and noise sensing. It is an important mechanism for building applications in the smart environments enabled by the internet-of-things. However, often a given problem may dictate that samples are drawn from a defined sub-population of participants, for example based on characteristics of the participant such as location, demographics or other profile attribute, rather than from any possible member of the whole population. In this article we introduce an approach for crowdsensing with a consideration for how to sample from specific sub-populations in a region, delineated in a dimension-based way analogous to the multi-dimensional data model used in data warehousing. Simulation and performance results are provided demonstrating the approach’s ability to maintain active participants, provide coverage of the region of interest, and to be able to scalably sample the variable of interest in relation to the sub-population. This is the first work to our knowledge to address and propose an approach to the specific problem of crowdsourcing from specific attribute-defined sub-populations.

Background Total hip arthroplasty (THA) is traditionally associated with a low complication rate, with complications such as infection, fracture and dislocation requiring readmission or reoperation. We seek to identify the complication rate among the anterior, direct lateral and posterior surgical approaches. Methods We reviewed all THAs performed at the Epworth Healthcare from 1 July 2014 to 30 June 2016. There were 2437 THAs performed by a variety of approaches. No hips were excluded from this study. We surveyed the hospital database and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify those patients who had been readmitted and/or reoperated on. Details collected included age, gender, laterality of the surgery (left/right/bilateral), surgical approach utilised, complications which occurred. Results There were 29 peri-prosthetic fractures detected (13 anterior, 9 lateral, 7 posterior) and 10 underwent revision of implant, 19 were fixed. The increased rate of revision in the anterior group was statistically significant. There were 14 dislocations (5 anterior, 1 lateral, 8 posterior) of which 8 prostheses were revised. Three cases operated via the anterior approach and 1 by the lateral had early subsidence without fracture, necessitating revision of the femoral prostheses. Operative site infection occurred in 12 cases (2 anterior, 4 lateral, 6 posterior) with 6 requiring revision of implants. Conclusion The complication rates between the 3 main approaches are similar, but individual surgeons should be vigilant for complications unique to their surgical approaches, such as femoral fractures in the anterior approach and dislocations in the posterior approach.

Background Head and neck squamous cell carcinoma (HNSCC) represents one of the most common malignancies worldwide with a high mortality rate mainly due to lack of early detection markers, frequent association with metastasis and aggressive phenotype. Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancers. The lncRNA prostate cancer-associated transcript 1 (PCAT-1) showed potential oncogenic roles in different cancers, however its role in HNSCC is not known. In this study, we evaluated the role of the PCAT-1 in HNSCC. Methods The expression of PCAT-1 was measured by quantitative real-time PCR in 23 paired human HNSCC tissues and adjacent non-tumor tissue specimens. Cell proliferation after depleting PCAT-1 was determined. Effect of PCAT-1 depletion in HNSCC cell lines was determined by qRT-PCR and Western blot analyses. Finally, JHU029 HNSCC cells was implanted subcutaneously into athymic nude mice and therapeutic potential of PCAT-1 was investigated. Results Up-regulation of PCAT-1 in TCGA dataset of HNSCC was noted. We also observed increased expression of PCAT-1 in archived HNSCC patient samples as compared to adjacent non-tumor tissues. Knockdown of PCAT-1 significantly reduced cell proliferation in HNSCC cell lines. Mechanistic study revealed significant down regulation of c-Myc and AKT1 gene in both RNA and protein levels upon knockdown of PCAT-1. We observed that c-Myc and AKT1 positively correlate with PCAT-1 expression in HNSCC. Further, we observed activation of p38 MAPK and apoptosis signal-regulating kinase 1 upon knockdown of PCAT-1 which induces Caspase 9 and PARP mediated apoptosis. Targeted inhibition of PCAT-1 regresses tumor growth in nude mice. Conclusion Together our data demonstrated an important role of the PCAT-1 in HNSCC and might serve as a target for HNSCC therapy.

In this article, we describe and evaluate a crowdsensing approach that entails local cooperation between crowdsensing participants in smart environments, utilizing an underlying fog computing-enabled Internet of Things. A fog computing-based Internet-of-Things architecture involves a layer of computing nodes residing closer to the sensing devices, with this layer of fog nodes lying in between mobile and sensing devices at the network edge and the cloud. This motivates us to propose a model for crowdsensing in smart environments that involves both competition and cooperation between nearby crowdsensing participants at the edge network. Comprehensive simulations are presented to evaluate the performance of the proposed approach. The work shows desirable characteristics in terms of number of active participants, number of samples collected within a given budget and coverage, resulting from localized cooperation by crowdsensing participants at the edge layer that can support various smart environment applications.

Background: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients. Methods: We used TaqMan low-density array (TLDA) qRT–PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion. Results: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial–mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells. Conclusions: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers.

Background: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. Methods: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. Results: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38). Conclusion: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

The information and communication technology infrastructure available in rural and remote areas may often not have the bandwidth to support all types of telehealth applications; therefore, for example, some traditionally envisaged videoconferencing-based telehealth applications may not be able to be used or not used in their anticipated form at this time. While the level of broadband services available may impose limitations on these types of telehealth applications, in this review article, we identify applications that allow the maximizing of telehealth benefits in the presence of low-bandwidth connectivity and have potential benefits well-matched to rural and remote area healthcare challenges. In particular, we include consideration of how ubiquitous computing might potentially bring non-traditional approaches to telehealth that can also come into usage more immediately in bandwidth-constrained rural and regional areas. In this article, we review the benefits of ubiquitous computing for rural and remote telehealth including social media-based preventative, peer support and public health communication, mobile phone platforms for the detection and notification of emergencies, wearable and ambient biosensors, the utilization of personal health records including in conjunction with mobile and sensor platforms, chronic condition care and management information systems, and mobile device---enabled video consultation.

Background: Recent research has shown that most of the excess risk of death following breast and colorectal cancer in England compared with Norway and Sweden occurs in older age groups during the first year, and especially in the first month of follow-up. The aim of this study was to explore the characteristics of patients dying within 30 days of being diagnosed with one of these cancers in Scotland during 2003–2007. Methods: Anonymised cancer registry records linked to hospital discharge and death records were extracted. The study population was divided into patients who died within 30 days of diagnosis (cases) and those who survived beyond this threshold (controls). Differences in patient-, tumour-, and health service-related characteristics were assessed using the χ2-test and logistic regression. Results: Patients dying within 30 days were more likely to be elderly and to have experienced emergency admission to non-surgical specialities. Their tumours were less likely to have been verified microscopically, but they appeared more likely to be of high grade and advanced in stage. A substantial number of patients died from causes other than their cancer. Conclusion: These results suggest that early mortality after a diagnosis of breast or colorectal cancer may be partly due to comorbidity and lifestyle factors, as well as due to more advanced disease. Further research is required to determine the precise explanation for these findings and, in particular, if any potentially avoidable factors such as delays in presentation, referral, or diagnosis exist.

The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.

Background: Response to EGFR-targeted therapies in colorectal cancer patients has been convincingly associated with Kirsten-Ras (K-Ras) mutation status. Current mandatory mutation testing for patient selection is limited to the K-Ras ‘hotspot' codons 12 and 13. Methods: Colorectal tumours (n=106) were screened for additional K-Ras mutations, phenotypes compared in transformation and Ras GTPase activating assays and gene and pathway changes induced by individual K-Ras mutants identified by microarray analysis. Taqman-based gene copy number and FISH analyses were used to investigate K-Ras gene amplification. Results: Four additional K-Ras mutations (Leu19Phe (1 out of 106 tumours), Lys117Asn (1 out of 106), Ala146Thr (7 out of 106) and Arg164Gln (1 out of 106)) were identified. Lys117Asn and Ala146Thr had phenotypes similar to the hotspot mutations, whereas Leu19Phe had an attenuated phenotype and the Arg164Gln mutation was phenotypically equivalent to wt K-Ras. We additionally identified a new K-Ras gene amplification event, present in approximately 2% of tumours. Conclusions: The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third. Future mutation screening to facilitate optimal patient selection for treatment with EGFR-targeted therapies should therefore be extended to codon 146, and in addition should consider the unique molecular signatures associated with individual K-Ras mutations.

Background MDT (multidisciplinary team) meetings are considered an essential component of care for patients with cancer. However there is remarkably little direct evidence that such meetings improve outcomes. We assessed whether or not MDT (multidisciplinary team) processes influenced survival in a cohort of patients with colorectal cancer. Methods Observational study of a population-based cohort of 586 consecutive patients with colorectal cancer diagnosed in Tayside (Scotland) during 2006 and 2007. Results Recommendations from MDT meetings were implemented in 411/586 (70.1 %) of patients, the MDT+ group. The remaining175/586 (29.9 %) were either never discussed at an MDT, or recommendations were not implemented, MDT- group. The 5-year cause-specific survival (CSS) rates were 63.1 % (MDT+) and 48.2 % (MDT-), p 6 weeks after diagnosis, the rates were 63.2 % (MDT+) and 57.7 % (MDT-), p = 0.064. The adjusted hazard rate (HR) for death from colorectal cancer was 0.73 (0.53 to 1.00, p = 0.047) in the MDT+ group compared to the MDT- group, in patients surviving >6 weeks the adjusted HR was 1.00 (0.70 to 1.42, p = 0.987). Any benefit from the MDT process was largely confined to patients with advanced disease: adjusted HR (early) 1.32 (0.69 to 2.49, p = 0.401); adjusted HR(advanced) 0.65 (0.45 to 0.96, p = 0.031). Conclusions Adequate MDT processes are associated with improved survival for patients with colorectal cancer. However, some of this effect may be more apparent than real – simply reflecting selection bias. The MDT process predominantly benefits the 40 % of patients who present with advanced disease and conveys little demonstrable advantage to patients with early tumours. These results call into question the current belief that all new patients with colorectal cancer should be discussed at an MDT meeting.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world. HNSCC remains difficult to treat, and despite advances in treatment, overall survival rate has modestly improved over the past several years. Poor survival rate is attributed to high frequency of local recurrence and distant metastasis. Cancer stem-like cells (CSCs) have been implicated in tumor recurrence and confer resistance to anti-cancer therapy treatment. In this study, we have characterized genes that are modulated in HNSCC-CSCs and can be targeted in future as potential therapeutics. CSCs were isolated from HNSCC cells (oralspheres) and examined for tumorigenicity in immunodeficient mice. We observed aggressive tumor growth with oralspheres as compared to parental cells. The CSC-derived tumors were grossly extremely vascularized and expressed VEGFR1. We next analyzed the molecular determinant of oralspheres. In addition to CD133 and Nanog, we observed significant higher expression of Notch1 protein in the oralspheres. There was differential expression of angiogenesis and invasive marker genes such as angiopoietin1, integrin β3, MMP9 and THBS1. Interestingly, c-Fos was upregulated in oralspheres as compared to parental cells. Our observations suggest that understanding the molecular determinant of oralspheres will help in developing future therapeutic modalities against treatment resistant HNSCC.

The aim of the study was to investigate expression of the active and inactive gelatinases (MMP-2 and -9) in colorectal neoplasia and gastric cancer compared with normal mucosa. A total of 53 colorectal cancers and corresponding normal mucosa were studied using gelatin zymography as well as 15 colorectal adenomas and 13 gastric cancers with corresponding normal mucosa. Overexpression of all the gelatinases occurs in both colorectal and gastric cancer, with activation of MMP-2 appearing to be a feature of the malignant phenotype. Overexpression of MMP-9 occurs in colorectal adenomas. The gelatinases are overexpressed in gastrointestinal neoplasia, suggesting that these enzymes may have an important role in tumour invasion and metastasis.

Several studies have provided strong, but indirect evidence that signalling through pathways involving protein kinase C (PKC) plays an important role in morphogenesis and patterning in Hydra. We have cloned a gene (HvPKC2) from Hydra vulgaris which encodes a member of the nPKC subfamily. In adult polyps, HvPKC2 is expressed at high levels in two locations, the endoderm of the foot and the endoderm of the hypostomal tip. Increased expression of HvPKC2 is an early event during head and foot regeneration, with the rise in expression being restricted to the endodermal cells underlying the regenerating ends. No upregulation is observed if regenerates are cut too close to the head to form a foot. Elevated expression of HvPKC2 is also observed in the endoderm underlying lithium-induced ectopic feet. A dynamic and complex pattern of expression is seen in developing buds. Regeneration of either head or foot is accompanied by an increase in the amount of PKC in both soluble and particulate fractions. An increase in the fraction of PKC activity which is membrane-bound is specifically associated with head regeneration. Taken together these data suggest that patterning of the head and foot in Hydra is controlled in part by the level of HvPKC2 expression, whilst head formation is accompanied by an in vivo activation of both calcium-dependent and independent PKC isoforms.

A gene encoding a receptor protein-tyrosine kinase closely related to the vertebrate insulin receptor has been identified in the Cnidarian Hydra vulgaris. The gene is expressed in both epithelial layers of the adult polyp. A particularly high level of expression is seen in the ectoderm of the proximal portions of the tentacles and in a ring of ectodermal cells at the border between the foot basal disk and body column. The expression pattern of the gene in asexual buds is dynamic; expression is high throughout the newly emerging bud but the area of high expression becomes restricted to the apex as the bud lengthens. When the bud begins hypostome and tentacle formation, a high level of expression appears at the bases of the emerging tentacles. Finally, a ring of high expression appears just above the foot of the bud, completing the pattern seen in the adult polyp. The presence of this receptor and its pattern of expression suggested that an endogenous molecule related to insulin plays a role in regulating cell division in the body column and in differentiation of the tentacle and foot cells in Hydra, with the switch between the two being determined by the level of the receptor. Treatment of Hydra polyps with mammalian insulin caused an increase in the number of ectodermal and endodermal cells undergoing DNA synthesis.

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition. Images Figure 1

Background Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second highest cause of cancer death in the UK. Most cases occur in people over 50 years and CRC often co-exists with other lifestyle related disorders including obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). These diseases share risk factors related to the metabolic syndrome including large body size, abnormal lipids and markers of insulin resistance indicating common aetiological pathways. Methods/Design This 3 year study will be a two-arm, multicentre, randomised controlled trial comparing the BeWEL lifestyle (diet, physical activity and behaviour change) programme against usual care. The pre-trial development will take 6 months and participants will be recruited over a 12 month period and undertake the intervention and follow up for 12 months (total 24 months recruitment and intervention implementation) with a further 6 months for data collection, analysis and interpretation. Four hundred and fifty two participants who have had a colorectal adenoma detected and removed (through the national colorectal screening programme) will provide 80% power to detect a weight loss of 7% over 12 months. Primary outcomes are changes in body weight and waist circumference. Secondary outcomes will include cardiovascular risk factors, psycho-social measures and intervention costs. Discussion The results from this study will enhance the evidence base for lifestyle change in patients at higher risk of chronic disease including obesity related cancers. International Standard Randomised Controlled Trials No: ISRCTN53033856

Ternary filters have tap values limited to , , or . This restriction in tap values greatly simplifies the multipliers required by the filter, making ternary filters very well suited to hardware implementations. Because they incorporate coarse quantisation, their performance is typically limited by tap quantisation error. This paper derives formulae for estimating the achievable performance of lowpass ternary filters, thereby allowing the number of computationally intensive design iterations to be reduced. Motivated by practical communications systems requirements, the performance measure which is used is the worst-case stopband attenuation.

The papers in this Special Issue particularly focus on the area of Business-to-Consumer Mobile Business. This issue of Personal and Ubiquitous Computing contains papers presented at the Fourth International Conference on Mobile Business (ICMB05) which was held in Sydney, Australia, 11–13 July 2005 and related papers. Eight of the contributions are extended versions of papers from ICMB05 and a further two papers are invited and peer-reviewed issue related papers. How the emerging Business-to-Consumer Mobile Business field will evolve is of great interest to the research community and to industry alike. However, a large number of disparate factors will affect which services will emerge and be widely adopted. Such factors include emerging mobile device capabilities and usability, perceived and actual security and privacy support, the economics of service provision and usage, future trends in content development, emerging network and provider capabilities and the role and place of mobile marketing amongst many others. The first two papers in the issue look at systems for close-range mobile interaction and advertising. The paper by Rashid, Coulton and Edwards presents a system for Location Based Advertising based on Bluetooth technology. The second paper by Moors, Mei and Salim describes a system for selectively controlling the functionality of mobile devices e.g., disabling mobile phone ringing in certain environments, via short-range communications capabilities. The next two papers examine different mobile interface issues. The paper by Chehimi, Coulton and Edwards considers current device constraints and probable future developments in the area of 3D mobile games (games with 3D graphics interfaces for use on mobile devices). The paper by Michelis, Resatsch, Nicolai and Schildhauer considers non-screen based interaction with mobile devices, particularly audible interfaces. The following two papers consider technical issues for mobile device connectivity. The paper by AliVehmas and Luukkainen considers enabling Push-toTalk capability over cellular networks. The next paper by Lin, Dillon and Wong considers a dynamic buffer size approach to enable more dependable location-aware information retrieval in a pervasive environment. The remaining four papers analyze adoption of mobile services from several perspectives. Mallat, Rossi, Tuunainen and OOrni consider study results from mobile ticketing adoption. The next paper by Koivumaki, Ristola and Kesti analyzes the effect of such factors as the familiarity of the mobile device, the duration of service use and user’s technology skills on mobile service usage experience and likelihood of continuous use. The paper by Wong and Hsu proposes a confidencebased framework for analyzing Business-to-Consumer, Mobile Commerce adoption. Finally, the paper by Heikkinen and Still analyzes the development of new mobile services from the perspective of business networks. R. Steele (&) Faculty of Information Technology, University of Technology, PO Box 123, Broadway, Sydney, NSW 2007, Australia e-mail: rsteele@it.uts.edu.au

Transanal local excision of posterior benign rectal tumors is usually safe. Here, we report a case of transanal excision of a posterior anastomotic recurrence of a rectal adenoma after a stapled anterior resection that resulted in perforation into the peritoneal cavity.

Immunohistochemical detection of epidermal growth factor receptors on human colonic carcinomas

Doctors who treat lung cancer in Ontario were previously asked how they would wish to be managed if they developed non-small cell lung cancer and whether they would consent to participate in six clinical trials for which they might be eligible. The proportion of these expert surrogate patients who would consent to each clinical trial ranged from 11 to 64%. The results of this study were transmitted to the same group of doctors who were asked to comment on the ethical acceptability of each trial in the light of this information. The majority of physicians said that those trials to which less than 50% of expert surrogates consented should not have been opened to patients. Sixty-nine per cent of doctors thought that new trials should be evaluated in this way. We also present the results of a survey of 400 lay people in Ontario who were asked to imagine that they had lung cancer and whether they would consent to participate in two of these same clinical trials. Fifty per cent of lay people consented to a randomised trial of lobectomy versus segmentectomy in early, operable disease (LCSC-821) compared to 64% of expert surrogates, and 48% of lay people consented to a randomised trial of five different forms of chemotherapy in metastatic disease (SWOG-8241) compared to 19% of doctors. It was concluded that the lay people were unable to discern differences in the acceptability of clinical trials which were clear to experts in the field. Subsequently, respondents were told about the decisions which doctors would make in the same circumstances and asked if this information would modify their previous decisions. There is no net change in the proportion of patients consenting to the surgery trial but the proportion of people consenting to the chemotherapy trial decreased by 40%. The majority of lay people said that they would wish to have access to this type of information before consenting to participate in a clinical trial.

Fifty estrogen receptor (ER)-positive breast cancers have been studied to determine the best way of correcting for differences in cellularity when expressing ER concentration. ER concentration expressed on wet weight and tumour cytosol protein bases showed a positive correlation with tumour cellularity. In contrast, ER concentrations expressed on a DNA basis were not significantly related to cellularity. Although such a mode of correcting for differences in cellularity was imperfect, it did yield a receptor concentration which was less dependent upon tissue cellularity and which may reflect more accurately the inherent receptor status of the tumour cells.

IN 1912, Mr. W. M. Voynich discovered in Italy a manuscript entirely written in cipher—a small quarto of 116 leaves, of which eight are missing and some are folded. It measures on the average about nine inches by six. Its history has many gaps, but Mr. Voynich is, we believe, right in his conjecture that it was sold by Dee to the Emperor Rudolph at the close of the sixteenth century, attributing it to Roger Bacon, and that it was probably “the book containing nothing but hieroglyphics” of which Dee's son spoke to Sir Thos. Browne. The usual methods of dating a MS. fail us: the writing cannot be placed, the vellum is coarse for the thirteenth century, but not impossible, the ink is good. Only the drawings remain, and owing to their complete absence of style the difficulty of dating is but increased; it is strange that the draughtsman should have so completely escaped all medieval or Renaissance influences. The cipher has been attacked by several experts in the ordinary methods, and has not yet been read. The Cipher of Roger Bacon. Prof. William Romaine Newbold. Edited with Foreword and Notes by Prof. Roland Grubb Kent. Pp. xxxii + 224 + 38 plates. (Philadelphia: University of Philadelphia Press; London: Oxford University Press, 1928.) 17s. net.

Plasma adriamycin and adriamycinol levels were measured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels as found. Plasma levels increased after the administration of each of the three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.

THE effect of hyperglycaemia on hepatic glucose output has been studied employing an isotope dilution technique. Glucose labelled with carbon-14, of the same specific activity as the blood glucose, was injected in amounts sufficient to produce hyperglycaemia. The selection of the appropriate specific activity for this glucose ‘load’ was made easier by a procedure in which an infusion of labelled glucose (in ‘weightless’ amount) was continued throughout the experiment. During such an experiment the blood glucose specific activity remains relatively constant so long as the flow of unlabelled glucose from the liver continues at a uniform rate. On the other hand, the specific activity of the blood glucose rises if the flow of unlabelled glucose from the liver stops or decreases1. The present technique avoids the misleading values for plasma glucose specific activity which might result from slow mixing of injected unlabelled glucose with a labelled body glucose pool1.

EVERY now and then a fresh attempt is made to solve this cipher attributed to Roger Bacon in the “Epistola de secretis operibus artis et natura et de nullitate magis” (see for example, NATURE, Sept. 4, 1926, p. 352). These words have no manuscript authority whatever; they appear for the first time in an edition of the “Epistola” printed in Paris in 1542 from a poor MS., and seem to be due to an attempt to reproduce the text before him by the editor, Orontius Fine. The passage reads thus

THE publication of a second part of Mrs. Singer's catalogue of alchemical manu scripts enables us to form some idea of its useful ness as a guide to the Corpus Scriftorum Alchemistarum, a usefulness which will be materially enhanced by a promised third part containing indexes of names, places, and first lines. It would be hard to exaggerate the importance of this work to the historian of scientific thought in western Europe; we are here put in possession of a key to the materials from which the story of the develop ment of alchemical theory can be written. Up to now, no historian of chemistry except Kopp, and in a lesser degree Berthelot, has gone to the manu script sources for his information; all of them, when they have not copied one from another, have aimlessly turned a few pages of the printed texts and extracted some sentences from them to small profit. The literature of alchemy was collected in the seventeenth century by Zetzner in six closely printed volumes and later by Manget in two folios? mainly from printed sources. The earliest treatises have in the main escaped printing down to our own days, while those of the early texts reproduced are incredibly corrupt by the accretion of notes and interlineations and by accidental omissions. But no thorough revision of the classics of Latin alchemy will be possible until the scholars of France and Italy have followed the example here set. In the meantime, any student of philosophy, equipped with some knowledge of the medieval Aristotle, will find here a rich field open to him. The catalogue is arranged in the order of the historic development of alchemical thought; first of treatises of Byzantine or Hellenic origin such as the "Turba Philosophorum", the "Emerald Table", and other treatises ascribed to Greek authors, real or apocryphal; then to Arabic authors, to Latin authors in prose, to anonymous treatises, to the large body of alchemical verse, to chemical crafts, and to receipts of all descriptions. The named treatises were included in the first part; the remainder are here given and their study throws an interesting light on the processes of chemical technology in the Middle Ages. One does not see how this arrangement can be improved upon, but it must not be allowed to mask the fact that alchemical theory in western Europe was entirely Arabist in its origin and growth. Chemical technology is purely Byzantine and Hellenic, but it was altogether divorced from theory, and the "Turba"is never quoted by any writer in the first century and a half of alchemical literature. But though Greek thought had no direct action on Latin writers, it was the ultimate source of Arabic alchemy as regards the theory of metals, the elixir of life being apparently of Chinese origin. No doubt a few Byzantine adepts found their way into the west?Roger Bacon mentions a Greek he had known, and there is the still earlier case of the Jew of Bremen. The story of translation from the Arabic begins with Robert of Chester in 1144, Plato of Tivoli and Hugo Sanctallensis, and goes on to Gerard of Cremona, who before his death in 1187 trans lated three classics of alchemy?two of them only printed in our own time, by Berthelot and the writer. A number of treatises were translated before the middle of the thirteenth century, as shown by the quotations from them in the "Speculum Naturale"of Vincent of Beauvais (1245), the alchemical writings of Roger Bacon ending 1267, and the writings of Albertus Magnus on minerals and the "Speculum Astronomicum". St. Thomas also accepts the scientific possibility of alchemy. The series of philosophic writers on alchemy closes with Arnold of Villanova at the end of the thirteenth century. Two expository works of some value as accounts of current theory were written in the first half of the fourteenth century?the "Margarita Novella"of Petrus Bonus and the "Quintessence"of Johannes de Rupescissa?but no new ideas are to be found in them; the developments of the Aristotelian theory of matter had been exhausted and the pursuit of the transmutation of metals had been abandoned, not as impossible but as impracticable. The fifteenth century brings in a spate of tracts, all with high-sounding claims, reiterating the old formula and clothed in the old mystification of language. It is impossible to rate too highly the unwearying industry of Mrs. Singer and her helpers; they have searched and almost re-catalogued not only the great collections of Sloane and Harley in the British Museum, of Digby and Ashmole at Oxford, but also every corner of every library, great or small, in Great Britain, and have revealed a scarcely suspected wealth of manuscripts. When their provenance is examined and tabulated some in teresting results may appear. It would seem that the earliest centre of alchemical activity was in northern Italy, that from there it spread to the south of France, thence to Paris, becoming common in England in the fourteenth century, as witness the "Canon's Yeoman's Tale"of Chaucer. Its progress is marked by the Act of 1403 making it illegal?alchemy had become a shield for coiners of false money. The Act, however, was powerless to stay the flood of students and treatises?some of them voluminous like those ascribed to Ramon Lull, which first appear in 1443 (translated from a non-existent Catalan original). There are, too, a number of official licences to practise alchemy on record, and more remarkable still, three Royal Commissions to inquire into its possibilities as a means of paying the King's debts?the last a very strong one consisting of four bishops and a number of high officials. It would be interesting if Mrs. Singer, who has ferreted out of the Record Office some alchemical tracts, could come upon the reports of these Commissions. Licences and treatises come to an end in England at the last quarter of the fifteenth century; 1476 for the licences, 1471 and 1477 for the treatises of Ripley and Norton. Commerce was offering a more certain road to wealth than alchemy. In the thousands of extracts of more or less barbarous Latin in badly written, badly spelled and contracted manuscripts here printed, it is not to be expected that there should be no doubtful readings; but speaking with no inconsiderable experience of medieval hands, I can say that the work as a whole would do credit to an expert palaeographer and bibliographer. It is the sort of work that only an enthusiast would undertake, and it betrays the hand of an amateur only in the desire for completeness which has led Mrs. Singer to give us lists of the manuscripts of the "Canterbury Tales"and such-like works which have been made the subject of intensive study elsewhere. Mrs. Singer and her assistants have earned the hearty thanks of all who are interested in the history of scientific thought. Union Academique Internationale. Catalogue of Latin and Vernacular Alchemical Manuscripts in Great Britain and Ireland dating from before the XVI. Century. Dorothea Waley Singer , assisted by Annie Anderson and Robina Addis. Vol. 2. Pp. viii + 329–755. (Brussels: Maurice Lamertin, 1930.) 10 Belgas.