Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003

Oriented Matroids -- Combinatorial Structures Underlying Loop Quantum Gravity

We analyze combinatorial structures which play a central role in determining spectral properties of the volume operator in loop quantum gravity (LQG). These structures encode geometrical information of the embedding of arbitrary valence vertices of a graph in 3-dimensional Riemannian space, and can be represented by sign strings containing relative orientations of embedded edges. We demonstrate that these signature factors are a special representation of the general mathematical concept of an oriented matroid. Moreover, we show that oriented matroids can also be used to describe the topology (connectedness) of directed graphs. Hence the mathematical methods developed for oriented matroids can be applied to the difficult combinatorics of embedded graphs underlying the construction of LQG. As a first application we revisit the analysis of [4-5], and find that enumeration of all possible sign configurations used there is equivalent to enumerating all realizable oriented matroids of rank 3, and thus can be greatly simplified. We find that for 7-valent vertices having no coplanar triples of edge tangents, the smallest non-zero eigenvalue of the volume spectrum does not grow as one increases the maximum spin \jmax at the vertex, for any orientation of the edge tangents. This indicates that, in contrast to the area operator, considering large \jmax does not necessarily imply large volume eigenvalues. In addition we give an outlook to possible starting points for rewriting the combinatorics of LQG in terms of oriented matroids.Comment: 43 pages, 26 figures, LaTeX. Version published in CQG. Typos corrected, presentation slightly extende

Earth BioGenome Project: Sequencing life for the future of life.

Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial

OBJECTIVE: To determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus (cCMV(-associated sensorineural hearing loss (SNHL). STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at United States (n=12) and United Kingdom (n=9) sites. Patients ages1 month through 3 years with baseline SNHL were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in CMV viral load in blood, saliva, and urine. RESULTS: Of 54 participants enrolled, 35 were documented to have cCMV infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) versus 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (p= 0.09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. CONCLUSIONS: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with cCMV-associated SNHL

From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke

<p>Abstract</p> <p>Background</p> <p>There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined.</p> <p>Methods/Design</p> <p>Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy.</p> <p>Discussion</p> <p>The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12608000042347.aspx">ACTRN12608000042347</a></p

Child mental health differences amongst ethnic groups in Britain: a systematic review

BACKGROUND: Inter-ethnic differences have been reported for many mental health outcomes in the UK, but no systematic review on child mental health has been published. The aim of this review is to compare the population-based prevalence of child mental disorders between ethnic groups in Britain, and relate these findings to ethnic differences in mental health service use. METHODS: A systematic search of bibliographic databases for population-based and clinic-based studies of children aged 0-19, including all ethnic groups and the main child mental disorders. We synthesised findings by comparing each minority group to the White British study sample. RESULTS: 31 population-based and 18 clinic-based studies met the inclusion criteria. Children in the main minority groups have similar or better mental health than White British children for common disorders, but may have higher rates for some less common conditions. The causes of these differences are unclear. There may be unmet need for services among Pakistani and Bangladeshi children. CONCLUSION: Inter-ethnic differences exist but are largely unexplained. Future studies should address the challenges of cross-cultural psychiatry and investigate reasons for inter-ethnic differences

A Genotyping Array for the Globally Invasive Vector Mosquito, Aedes albopictus

BACKGROUND: Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising up to 72% repetitive elements, and therefore we set out to develop a single-nucleotide polymorphism (SNP) chip to be more cost-effective. Aedes albopictus is an invasive species originating from Southeast Asia that has recently spread around the world and is a vector for many human diseases. Developing an accessible genotyping platform is essential in advancing biological control methods and understanding the population dynamics of this pest species, with significant implications for public health. METHODS: We designed a SNP chip for Ae. albopictus (Aealbo chip) based on approximately 2.7 million SNPs identified using WGS data from 819 worldwide samples. We validated the chip using laboratory single-pair crosses, comparing technical replicates, and comparing genotypes of samples genotyped by WGS and the SNP chip. We then used the chip for a population genomic analysis of 237 samples from 28 sites in the native range to evaluate its usefulness in describing patterns of genomic variation and tracing the origins of invasions. RESULTS: Probes on the Aealbo chip targeted 175,396 SNPs in coding and non-coding regions across all three chromosomes, with a density of 102 SNPs per 1 Mb window, and at least one SNP in each of the 17,461 protein-coding genes. Overall, 70% of the probes captured the genetic variation. Segregation analysis found that 98% of the SNPs followed expectations of single-copy Mendelian genes. Comparisons with WGS indicated that sites with genotype disagreements were mostly heterozygotes at loci with WGS read depth \u3c 20, while there was near complete agreement with WGS read depths \u3e 20, indicating that the chip more accurately detects heterozygotes than low-coverage WGS. Sample sizes did not affect the accuracy of the SNP chip genotype calls. Ancestry analyses identified four to five genetic clusters in the native range with various levels of admixture. CONCLUSIONS: The Aealbo chip is highly accurate, is concordant with genotypes from WGS with high sequence coverage, and may be more accurate than low-coverage WGS

Evaluating the effectiveness of agricultural adaptation to climate change in preindustrial society

The effectiveness of agricultural adaptation determines the vulnerability of this sector to climate change, particularly during the preindustrial era. However, this effectiveness has rarely been quantitatively evaluated, specifically at a large spatial and long-term scale. The present study covers this case of preindustrial society in AD 1500–1800. Given the absence of technological innovations in this time frame, agricultural production was chiefly augmented by cultivating more land (land input) and increasing labor input per land unit (labor input). Accordingly, these two methods are quantitatively examined. Statistical results show that within the study scale, land input is a more effective approach of mitigating climatic impact than labor input. Nonetheless, these observations collectively improve Boserup's theory from the perspective of a large spatial and long-term scale.postprin