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Journal of Instrumentation 15(09), P09004 (2020). doi:10.1088/1748-0221/15/09/P09004, For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2,2] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests., Published by Inst. of Physics, London

The scaling of reaction yields in light ion fusion to low reaction energies is important for our understanding of stellar fuel chains and the development of future energy technologies. Experiments become progressively more challenging at lower reaction energies due to the exponential drop of fusion cross sections below the Coulomb barrier. We report on experiments where deuterium-deuterium (D-D) fusion reactions are studied in a pulsed plasma in the glow discharge regime using a benchtop apparatus. We model plasma conditions using particle-in-cell codes. Advantages of this approach are relatively high peak ion currents and current densities (0.1 to several A/cm2) that can be applied to metal wire cathodes for several days. We detect neutrons from D-D reactions with scintillator-based detectors. For palladium targets, we find neutron yields as a function of cathode voltage that are over 100 times higher than yields expected for bare nuclei fusion at ion energies below 2 keV (center of mass frame). A possible explanation is a correction to the ion energy due to an electron screening potential of 1000 ± 250 eV, which increases the probability for tunneling through the repulsive Coulomb barrier. Our compact, robust setup enables parametric studies of this effect at relatively low reaction energies., United States. Department of Energy. (Contract DE-AC02-05CH11231)

Background— The aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin. Methods and Results— We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P P =0.001), and improved net clinical benefit (adjusted P P =0.082 for ischemic stroke and adjusted P =0.109 for major hemorrhage). Conclusions— In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00041938.

CD248 (endosialin) is a transmembrane glycoprotein that is dynamically expressed on pericytes and fibroblasts during tissue development, tumour neovascularization and inflammation. Its role in tissue remodelling is associated with increased stromal cell proliferation and migration. We show that CD248 is also uniquely expressed by human, but not mouse (C57BL/6), CD8(+) naive T cells. CD248 is found only on CD8(+) CCR7(+) CD11a(low) naive T cells and on CD8 single-positive T cells in the thymus. Transfection of the CD248 negative T-cell line MOLT-4 with CD248 cDNA surprisingly reduced cell proliferation. Knock-down of CD248 on naive CD8 T cells increased cell proliferation. These data demonstrate opposing functions for CD248 on haematopoietic (CD8(+)) versus stromal cells and suggests that CD248 helps to maintain naive CD8(+) human T cells in a quiescent state.

Studies of stromal cell populations in lymphoid tissue (LT) have been hampered by a lack of selective markers. Here, we show that CD248 (Endosialin/TEM1) is a stromal marker that is differentially expressed on fibroblasts and pericytes in the thymus, lymph node and spleen. Expression is high during LT development but largely disappears in the adult. CD248 is re-expressed in a Salmonella-induced model of splenic enlargement; peak expression corresponding to the peak of splenic enlargement. These results suggest that CD248 expression helps define a subset of LT stromal cells which play a role in remodelling during tissue development, infection and repair.

Endosialin has been assigned the alternate name of tumour endothelial marker 1 (TEM1) due to its identification as a highly upregulated gene transcript in tumour endothelium compared to normal endothelium. As a consequence there is interest in endosialin as a potential therapeutic target in cancer treatment. However, there are conflicting reports over the nature of vascular expression in tumours with some evidence that endosialin is expressed on perivascular pericytes rather than the endothelial cells themselves. To address this, we have analysed the expression of endosialin in mouse embryos, newborn pups and adults. In the embryo endosialin is predominantly expressed on stromal fibroblasts throughout the mesenchyme but expression is also observed on the developing vasculature. When analysed by confocal microscopy endosialin on vessels does not colocalise with endothelial cells expressing CD31. Rather, endosialin is restricted to closely associated perivascular cells that also express the pericyte marker NG2. Finally, the fibroblast and pericyte expression of endosialin changes dynamically during development and becomes highly restricted in adult mouse tissues. This evolving picture of endosialin expression in sites of active tissue remodelling and neovascularisation has implications in tumour growth, angiogenesis and metastasis.

Endo180, also known as the urokinase plasminogen activator receptor (uPAR)-associated protein (uPARAP), is one of the four members of the mannose receptor family, and is implicated in extracellular-matrix remodelling through its interactions with collagens, sugars and uPAR. The extracellular portion of Endo180 contains an amino-terminal cysteine-rich domain, a single fibronectin type II domain and eight C-type lectin-like domains. We have purified a soluble version of Endo180 and analysed it by single-particle electron microscopy to obtain a three-dimensional structure of the N-terminal part of the protein at a resolution of 17 Å and reveal, for the first time, the interactions between non-adjacent domains in the mannose receptor family. We show that for Endo180, the cysteine-rich domain contacts the second C-type lectin-like domain, thus providing structural insight into how modulation of its several ligand interactions may regulate Endo180 receptor function.

This study was designed to compare different proposed methods of assessing adherence with angiotensin-converting enzyme (ACE) inhibitor (ACEI) therapy in chronic heart failure.The use of ACEIs in chronic heart failure gives us a unique opportunity to assess a patient's adherence by measuring whether the expected biochemical effect of an ACEI is present in the patient's bloodstream. In fact, there are several different ways of assessing ACE in vivo: these are serum ACE activity itself, plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), urine AcSDKP, plasma angiotensin I (AI), plasma angiotensin II (AII), or the AII/AI ratio.Patients with chronic heart failure (n = 39) were randomized to regimens of ACEI nonadherence for one week, ACEI adherence for one week or two versions of partial adherence for one week, after which the above six tests were performed.All six tests significantly distinguished between full nonadherence for one week and full or partial adherence. Only plasma AcSDKP produced a significantly different result between partial adherence and either full adherence or full nonadherence for one week. In terms of their ability to distinguish full nonadherence from full adherence, plasma AcSDKP was 89% sensitive and 100% specific with an area under its ROC of 0.95. Corresponding figures for urine AcSDKP were 92%, 97% and 0.95 and for serum ACE they were 86%, 95% and 0.90.All six tests distinguished full nonadherence from all other forms of adherence. The rank order of performance was plasma AcSDKP, urine AcSDKP, serum ACE, AII/AI ratio and plasma AII followed by plasma AI.

Till recently, it does not seem to have occurred to anyone that there was a fatal defect in the usual mode of estimating a life company's expenditure, and we were content to go on in the old way of considering it as the ratio such expenditure bore to the total premium revenue. And, so far as my recollection goes, not even the offices that had been animadverted on for extravagance, thought fit to dispute the dictum on the ground that this method of calculation was erroneous. However, since the reading of Mr. Deuchar's paper, and the more recent publication of Mr. Sprague's letters, these societies have awakened to the fact that they have been much calumniated; and are now ready, as a complete answer to the charge, to point out that it is their new business that has cost the money. No doubt this is a perversion of their theory that Messrs.

Referring to Mr. Sprague's reply to the Discussion on his paper (J. I. A.xix, 324), I would wish to point out that the admission by me, that a company, for its own internal purposes, may discriminate between expenditure on old and on new business, is not an admission of the principle which Mr. Sprague contends for. It required no argument to show that when an office wished to know what its new business was costing, it would be requisite for it to disentangle the expenditure on new business from general outlay. It is no conversion to Mr. Sprague's views to admit this. The point between us is not that, but the more complex one of thecommonmeasure to apply to outlay on all business, both old and new.

There is nothing immutable in this world, and certainly life companies are no exception to the general rule; for in them, from year to year, we find fluctuations of every kind—in amount of new assurances—in expenses of management—in value of assets—in realized interest—in the death claims—in fact, in every branch and item of their business. Of all these variations there is none so important as that concerning the mortality experienced. The fluctuations in the other elements of a life office's affairs are trifling as compared with this, and can without difficulty be prepared for. But in the perturbations of the death claims from year to year, we are dealing with a matter that cannot be calculated on in advance —an element which, if violent, may endanger the safety of the company itself; and, even when this is not the case, will often prove a serious inconvenience to it. I have called violent mortality fluctuations inconvenient to a life office. To men acquainted with the practical as well as the theoretical side of assurance, the word will not seem exaggerated. They, at least, know how important it is that the bonus to policyholders and the dividend to shareholders, do not retrograde. The moment the bonus tide begins to ebb, there is an outcry; and variations in the mortality may thus create disgust in those already connected with an office, and at the same time add another difficulty to the already sufficiently difficult task of its agents and canvassers.

Some years ago I had the honour of reading before this Institute a paper which, though mainly devoted to a study of surrender values, treated such surrender values as purchases by life offices of reversions. On that occasion I stated that sound British companies could well afford to repurchase their own acceptances at 6 or even at 5 per-cent. Subsequent experience has done much to confirm me in the opinion then expressed, but I did not then, nor do I now assert that offices should on such terms purchase other reversions than their own policies; and I trust it will not be thought wasting your time, if I preface this paper by enumerating a few considerations which seem to indicate that the present market price of reversions gives, comparatively, a return none too high to an investor. Such market rate I take to be 5 per-cent in the case of an investor who does not stand, or, what is the same thing, arrives at his price as if he did not intend to stand, any risk of loss, whether through longevity of life tenant or death of reversioner.

With the exception perhaps of extra premium, there is, it seems to me, no actuarial point in which the practice of assurance offices is so empirical as that of the allowance to be given for the surrender of a policy. The usual custom, so far as I am aware, is to find the value of the policy (generally by the table of mortality and interest used in calculating the reserve) and from that value to deduct a certain proportion, handing over the remainder to the policyholder. The amount of this deduction is purely arbitrary, and were it not for the equalizing effects of competition, would show very startling diversities; since, even with this counteracting effect, the differences in practice can hardly help striking anyone who has examined the amounts given as surrender value by the various offices interested in large reassurance cases which from any reason do not follow the rule of the parent company. In fact, making any return whatever under discontinued policies is the result of that struggle for existence called competition; and like all things growing from this root, the practice has been moulded much more by the pressure of circumstances than by theoretical considerations. Consequent on this method of growth we find extraordinary and indefensible anomalies imperatively calling for rectification. Further it seems to me, looking at the matter as a purely practical question and not one of actuarial fitness at all, there is no point more needful of examination. As things are at present, nobody can say positively whether as its proportion of the value the assurance office retains too little or too much. If the former, the sooner a practice resulting in loss is reformed, the better.

The question with which I have headed this paper is one that may seem startling enough. It has been so widely taken for granted that a large new business must be an unmixed good to all concerned in a life company, that to debate whether it be so or no, will seem in the eyes of many to be a very idle thing. And yet, though I have been considering the subject for a long time, I cannot answer the question unhesitatingly in the affirmative. In saying this, it ought to be pointed out, that the matter is regarded from a purely practical point of view. The problem is not ought a large new business to benefit policyholders? but, as a matter of fact, does it? Even if the question were answered in the negative, it would not follow that no new business, or an insufficient quantity of it, would better suit the interests of the policyholders. Waste must be supplied, and a certain degree of magnitude maintained in life companies.

A paper on Extra Premium may treat of the subject in one or other of two ways. It may be, on the one hand, an attempt to deduce tables of mortality for the various classes of under-average risks occurring in a Life Office's transactions. Or, on the other hand, this part of the subject may be ignored and the paper be simply an enquiry into the effects resulting from the various methods employed in charging extra—an analysis of the actuarial points raised in consequence of a Society admitting not merely minimum risk lives, but others not eligible on similar terms. In short, the subject of Extra Premium may be considered either in respect to the amount to be imposed or in regard to the manner and effect of its imposition. The first question must be determined mainly by actual mortality observations—the second does not require in the same degree for its examination the light of experience. It is this latter question which I have taken up in the following paper; but as both branches of the subject are intimately connected, it may be well to make a few general remarks on the former also.

Fibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly. We demonstrate conclusively that endosialin is a cell surface glycoprotein and is predominantly expressed by fibroblasts and a subset of pericytes associated with tumour vessels but not by tumour endothelium. These novel antibodies will facilitate the isolation and classification of fibroblast and pericyte lineages as well as the further functional analysis of endosialin.

The application of bonus to the hastening of the time fixed by the original contract for the payment of a life assurance policy, and the using of it to extinguish the premiums payable during the latter years of life, are systems, which, partly from their growing favor with the public, and consequent adoption by many offices, and still more from the fact, that the subject is by no means exhausted, notwithstanding various able articles that have appeared in this Journal, seem to me to render apology unnecessary for again treating of it.