Removing Orbital Debris with Lasers

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

Wigner Crystalline Edges in nu < 1 Quantum Dots

We investigate the edge reconstruction phenomenon believed to occur in quantum dots in the quantum Hall regime when the filling fraction is nu < 1. Our approach involves the examination of large dots (< 40 electrons) using a partial diagonalization technique in which the occupancies of the deep interior orbitals are frozen. To interpret the results of this calculation, we evaluate the overlap between the diagonalized ground state and a set of trial wavefunctions which we call projected necklace (PN) states. A PN state is simply the angular momentum projection of a maximum density droplet surrounded by a ring of localized electrons. Our calculations reveal that PN states have up to 99% overlap with the diagonalized ground states, and are lower in energy than the states identified in Chamon and Wen's study of the edge reconstruction.Comment: 8 pages, 8 figures, to be published in Phys. Rev.

APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

<p>Abstract</p> <p>Background</p> <p>5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets.</p> <p>Methods</p> <p>Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified.</p> <p>Results</p> <p>APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set. Stratified analysis revealed that protein expression of APRIL in the tumour stroma is associated with survival in adjuvant 5FU treated patients only (n = 103, p < 0.001), and is independently predictive of lack of clinical benefit from adjuvant 5FU [HR 6.25 (95%CI 1.48-26.32), p = 0.013].</p> <p>Conclusions</p> <p>A combined investigative model, analysing the transcriptional response in clinical tumour specimens and cancers cell lines, has identified APRIL, a novel chemo-resistance biomarker with independent predictive impact in 5FU-treated CRC patients, that may represent a target for novel therapeutics.</p

A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition

IntroductionThere is an emerging need for plant-based, vegan options for patients requiring nutritional support.MethodsTwenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed.ResultsPatients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition (‘MUST’ score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p &lt; 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p &gt; 0.06) with no serious adverse events related.DiscussionThis study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition

Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial

Summary: Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more eff ective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more eff ective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and effi cacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m², l-folinic acid 175 mg, fl uorouracil 400 mg/m² bolus, then 2400 mg/m² by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the fi rst 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratifi cation variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no signifi cant diff erences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had complications prolonging hospital stay (p=0·81). 98% (50 of 51) of postoperative chemotherapy patients had T3 or more advanced tumours confi rmed at post-resection pathology compared with 91% (90 of 99) of patients following preoperative chemotherapy (p=0·10). Preoperative therapy resulted in signifi cant downstaging of TNM5 compared with the postoperative group (p=0·04), including two pathological complete responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p<0·0001), resection margin involvement (4% [ four of 99] vs 20% [ten of 50], p=0·002), and blinded centrally scored tumour regression grading: 31% (29 of 94) vs 2% (one of 46) moderate or greater regression (p=0·0001). Interpretation Preoperative chemotherapy for radiologically staged, locally advanced operable primary colon cancer is feasible with acceptable toxicity and perioperative morbidity. Proceeding to the phase 3 trial, to establish whether the encouraging pathological responses seen with preoperative therapy translates into improved long-term oncological outcome, is appropriate

"Linkages Between the Concepts of 'Subsidiarity' and Sovereignty: The New Debate Over Allocation of Authority in the European Union"

It is our thesis that there is an important linkage between the concepts of sovereignty and subsidiarity. The democratization of the concept of sovereignty, introducing the idea of popular sovereignty, makes it closely linked to the concept of subsidiarity which has been given great notoriety in the current debate about future authority relations within the European Union. It is our general contention that the issues addressed in the current subsidiarity debate can be reconstructed and reinterpreted as a euphemism for the sovereignty debate which has been ongoing since the formation of the European Coal and Steel Community in the early 1950's. The subject will be introduced by a comparative review of the connotations of sovereignty and subsidiarity at various periods since the formation of the modern states-system. The core of the study is an examination of linkages between contemporary connotations of sovereignty and the current discourse about the subsidiarity principle. The official British public debates over sovereignty in connection with 1) its first application for membership in the early 1960's, 2) the membership ratification debate in 1972, 3) the referendum on continued membership in 1975, and 4) the ratification of Maastricht in 1992-1993 are used as a case study to demonstrate linkages between sovereignty and subsidiarity

The effects of temporal aggregation of data in forecasting macro-economic relations

Typescript (photocopy).The economist is often forced, by availability, to use data which is aggregated over time. In this study the effects of using temporally aggregated data in estimating and predicting economic relations is assessed. As an example the Michigan Quarterly Econometric Model (MQEM) of the U.S. economy is used. Assuming MQEM is the "true" specification of the Model the effects of aggregating the Model and the data to an annual model in estimation and prediction is evaluated. The bias implied by the aggregation process tends to be most severe when lagged endogenous as well as exogenous values are used, and does not pose much of a problem when no lag values exist in a given equation. In fact the magnitude of the estimated coefficients change very little in this latter case. The true problem is a specification bias that enters when temporally aggregated data is used when our equations involve lag values. Although the existence of an aggregation bias poses problems in finding the "true" structural parameters; the results of this study indicate that temporal aggregation causes only slight deterioration of predictive performance

Balloon warriors for North Korean human rights activism: a critique of North Korean defector-activists??? post-humanitarianism

While the identity politics of North Korean defector-activists at home and abroad is revealed by unraveling the discursive complexity of their activism, little attention has been paid to the way in which that activism compromises the discursive dynamic of the defector community desiring to contest the power of a ruling paradigm within political culture. A critical analysis of North Korean defector balloon warriors who have crusaded against the North Korea regime through airborne leaflet drops at the South???North Korea border illustrates how their uncritical and unquestioned acceptance of liberal human rights can only leave the defector community vulnerable to charges of being politically-futile disparate citizens. The invocations of transnational liberal hegemonic norms obscure and undermine North Korean defectors??? agency of collective engagement in acts of liberal democratic citizenship. Understanding the propagandistic dimension of their dissenting voices can help expand the scope of analysis of liberal democratic posthumanitarian citizenship