FINDCHIRP: an algorithm for detection of gravitational waves from inspiraling compact binaries

Matched-filter searches for gravitational waves from coalescing compact binaries by the LIGO Scientific Collaboration use the FINDCHIRP algorithm: an implementation of the optimal filter with innovations to account for unknown signal parameters and to improve performance on detector data that has nonstationary and non-Gaussian artifacts. We provide details on the FINDCHIRP algorithm as used in the search for subsolar mass binaries, binary neutron stars, neutron star-black hole binaries, and binary black holes.Comment: 19 pages, 1 figure, journal version with Creative Commons 4.0 open-access license adde

Decision making in NICE single technological appraisals (STAs): How does NICE incorporate patient perspectives?

The National Institute for Health and Care Excellence (NICE) provides guidance and recommendations on the use of new and existing medicines and treatments within the NHS, basing its decisions on a review of clinical and economic evidence principally, at least for STAs, provided by the drug manufacturer. The advice provided by NICE is aimed at overcoming the previously ad hoc, discretionary decisions in order to standardise access to healthcare technologies across England based on evidence. A Single Technological Appraisal (STA) is one element of NICE’s decision-making processes in which evidence about a selected technology (often medicines) is evaluated in 3 distinct phases (scoping, assessment and appraisal). In the last phase of this process an independent Appraisal Committee evaluates evidence in a meeting, partly held in public with the latter half taking place in a ‘closed’ session. During the meeting, the Appraisal Committee considers evidence based on clinical and cost-effectiveness, as well as from statements expressed by patients, commissioning experts and clinical specialists. The Institute encourages experts attending the meeting to provide both written and oral commentary about their personal view in the current management of the condition and the expected role and use of the technology – in particular how it might provide benefit to patients. Yet, NICE and its committees find themselves in a potentially incongruous position: how to take on board the experiential evidence from individual experts along with the evidence on cost-effectiveness when reaching a decision, about whether or not to recommend a treatment on cost-effectiveness grounds. This paper considers how NICE committees incorporate the views of patient perspectives in making rationing decisions about STAs. The findings from the study will discuss where points of tension / conflict arise during meetings and how Committee members navigate experiential accounts with scientific data, which types of patient perspectives are regarded favourably and which perspectives are treated with greater caution (tension between representing patients views vs tokenism), and will highlight how Committee members in fact reflect upon their own personal experience and background in the appraisal process, and thereby are at odds with retaining an element of neutrality in decision-making, as they contend with combining their own subjective views alongside considerations of rationing in the STA process. The analysis is drawn from an ESRC funded study which used an ethnographic approach to understand the decision making process within STAs involving three contrasting pharmaceutical products. Data collection methods included analysis of documentary evidence released by NICE, non-participant unstructured observations of nine STA meetings, and qualitative interviews with key informants (n=41) involved in each of the three case studies

The Self-Taught Marketers Guide to Creating an Annual Report

Objective To produce an easy-to-read, visually appealing, 1-4 page annual report for the University of Maryland, Baltimore’s Health Sciences and Human Services Library (HSHSL). The report should be a mix of interesting statistics, highlights, stories, quotes, and photographs to promote the HSHSL’s annual accomplishments to the campus. Methods We gather all of the stories and statistics we think will be eligible material for the annual report, pulling content and ideas from: newsletters, workshops, blog posts, events, exhibits, and meetings with division and department heads. An annual report committee and visual designer decide upon the top stories and statistics, focusing upon high-impact events, meaningful statistics, and attractive design, images, and photographs to craft the report. We keep in mind that the report is meant to be read by non-librarians, and that the language and messages need to be understandable to our larger campus community.Results This will be our 5th year producing an annual report for the HSHSL. The process has become more streamlined and less time-consuming as we have become familiar with where to source content, design principles, and how to manage space limitations. This has decreased the amount of time it takes to produce the report and the number of iterations we go through before achieving our final product. Additionally, other libraries have been inspired by our designs and created their own colorful Annual Reports based on our layouts and ideas. Conclusions In our next report we plan to include a survey link to try to elicit feedback from our readers. We would like to know if the report was useful to them and if there is other information they would be interested to see in future reports

Age-related mitochondrial DNA depletion and the impact on pancreatic beta cell function

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes

Evolutionary relationships of Aurora kinases: Implications for model organism studies and the development of anti-cancer drugs

BACKGROUND: As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family. RESULTS: Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A. CONCLUSIONS: In this study, we found that invertebrate Aurora-A and Aurora-B kinases are highly divergent protein families from their chordate counterparts. Furthermore, while the Aurora-A family is ubiquitous among all vertebrates, the Aurora-B and Aurora-C families in humans arose from a gene duplication event in mammals. These findings show the importance of understanding evolutionary relationships in the interpretation and transference of knowledge from studies of model organism systems to human cellular biology. In addition, given the important role of Aurora kinases in cancer, evolutionary analysis and comparisons of ATP-binding domains suggest a rationale for designing dual action anti-tumor drugs that inhibit both Aurora-B and Aurora-C kinases

A Dark Spot on a Massive White Dwarf

We present the serendipitous discovery of eclipse-like events around the massive white dwarf SDSS J152934.98+292801.9 (hereafter J1529+2928). We selected J1529+2928 for time-series photometry based on its spectroscopic temperature and surface gravity, which place it near the ZZ Ceti instability strip. Instead of pulsations, we detect photometric dips from this white dwarf every 38 minutes. Follow-up optical spectroscopy observations with Gemini reveal no significant radial velocity variations, ruling out stellar and brown dwarf companions. A disintegrating planet around this white dwarf cannot explain the observed light curves in different filters. Given the short period, the source of the photometric dips must be a dark spot that comes into view every 38 min due to the rotation of the white dwarf. Our optical spectroscopy does not show any evidence of Zeeman splitting of the Balmer lines, limiting the magnetic field strength to B<70 kG. Since up to 15% of white dwarfs display kG magnetic fields, such eclipse-like events should be common around white dwarfs. We discuss the potential implications of this discovery on transient surveys targeting white dwarfs, like the K2 mission and the Large Synoptic Survey Telescope.Comment: ApJ Letters, in pres

Spitzer Space Telescope Spectroscopy of Ices toward Low-Mass Embedded Protostars

Sensitive 5-38 μm Spitzer Space Telescope and ground-based 3-5 μm spectra of the embedded low-mass protostars B5 IRS1 and HH 46 IRS show deep ice absorption bands superposed on steeply rising mid-infrared continua. The ices likely originate in the circumstellar envelopes. The CO_2 bending mode at 15 μm is a particularly powerful tracer of the ice composition and processing history. Toward these protostars, this band shows little evidence for thermal processing at temperatures above 50 K. Signatures of lower temperature processing are present in the CO and OCN^- bands, however. The observed CO2 profile indicates an intimate mixture with H_(2)O, but not necessarily with CH_(3)OH, in contrast to some high-mass protostars. This is consistent with the low CH_(3)OH abundance derived from the ground-based L-band spectra. The CO_2 : H_(2)O column density ratios are high in both B5 IRS1 and HH 46 IRS (~35%). Clearly, the Spitzer spectra are essential for studying ice evolution in low-mass protostellar environments and for eventually determining the relation between interstellar and solar system ices

Periodic optical variability and debris accretion in white dwarfs: a test for a causal connection

Recent Kepler photometry has revealed that about half of white dwarfs (WDs) have periodic, low-level (~ 1e-4 - 1e-3), optical variations. Hubble Space Telescope (HST) ultraviolet spectroscopy has shown that up to about one half of WDs are actively accreting rocky planetary debris, as evidenced by the presence of photospheric metal absorption lines. We have obtained HST ultraviolet spectra of seven WDs that have been monitored for periodic variations, to test the hypothesis that these two phenomena are causally connected, i.e. that the optical periodic modulation is caused by WD rotation coupled with an inhomogeneous surface distribution of accreted metals. We detect photospheric metals in four out of the seven WDs. However, we find no significant correspondence between the existence of optical periodic variability and the detection of photospheric ultraviolet absorption lines. Thus the null hypothesis stands, that the two phenomena are not directly related. Some other source of WD surface inhomogeneity, perhaps related to magnetic field strength, combined with the WD rotation, or alternatively effects due to close binary companions, may be behind the observed optical modulation. We report the marginal detection of molecular hydrogen in WD J1949+4734, only the fourth known WD with detected H_2 lines. We also re-classify J1926+4219 as a carbon-rich He-sdO subdwarf.Comment: MNRAS, in pres

A method for reducing animal use whilst maintaining statistical power in electrophysiological recordings from rodent nerves

The stimulus evoked compound action potential, recorded from ex vivo nerve trunks such as the rodent optic and sciatic nerve, is a popular model system used to study aspects of nervous system metabolism. This includes (1) the role of glycogen in supporting axon conduction, (2) the injury mechanisms resulting from metabolic insults, and (3) to test putative benefits of clinically relevant neuroprotective strategies. We demonstrate the benefit of simultaneously recording from pairs of nerves in the same superfusion chamber compared with conventional recordings from single nerves. Experiments carried out on mouse optic and sciatic nerves demonstrate that our new recording configuration decreased the relative standard deviation from samples when compared with recordings from an equivalent number of individually recorded nerves. The new method reduces the number of animals required to produce equivalent Power compared with the existing method, where single nerves are used. Adopting this method leads to increased experimental efficiency and productivity. We demonstrate that reduced animal use and increased Power can be achieved by recording from pairs of rodent nerve trunks simultaneously