Multimodal optical characterisation of collagen photodegradation by femtosecond infrared laser ablation.

Collagen is a structural component of the human body, as a connective tissue it can become altered as a result of pathophysiological conditions. Although the collagen degradation mechanism is not fully understood, it plays an important role in ageing, disease progression and applications in therapeutic laser treatments. To fully understand the mechanism of collagen alteration, in our study photo-disruptive effects were induced in collagen I matrix by point-irradiation with a femtosecond Ti-sapphire laser under controlled laser ablation settings. This was followed by multi-modal imaging of the irradiated and surrounding areas to analyse the degradation mechanism. Our multi-modal methodology was based on second harmonic generation (SHG), scanning electron microscope (SEM), autofluorescence (AF) average intensities and the average fluorescence lifetime. This allowed us to quantitatively characterise the degraded area into four distinct zones: (1) depolymerised zone in the laser focal spot as indicated by the loss of SHG signal, (2) enhanced crosslinking zone in the inner boundary of the laser induced cavity as represented by the high fluorescence ring, (3) reduced crosslinking zone formed the outer boundary of the cavity as marked by the increased SHG signal and (4) native collagen. These identified distinct zones were in good agreement with the expected photochemical changes shown using Raman spectroscopy. In addition, imaging using polarisation-resolved SHG (p-SHG) revealed both a high degree of fibre re-orientation and a SHG change in tensor ratios around the irradiation spot. Our multi-modal optical imaging approach can provide a new methodology for defining distinct zones that can be used in a clinical setting to determine suitable thresholds for applying safe laser treatments without affecting the surrounding tissues. Furthermore this technique can be extended to address challenges observed in collagen based tissue engineering and used as a minimally invasive diagnostic tool to characterise diseased and non-diseased collagen rich tissues

Recent increases in Tasmanian Huon pine ring widths from a subalpine stand: natural climate variabiliry, CO2 fertilisation, or greenhouse warming?

Tasmanian subalpine Huon pines from the extreme high-altitude limit of the species distribution provide a summer temperature reconstruction extending back beyond 800 BC. Compared to low elevation Huon pine sites, the subalpine ring-widths exhibit a straightforward direct response to current growth-season temperatures and indicate anomalous warming of 0.33 ± O.06°C from 1967-91. This warming is consistent with Tasmanian instrumental records and with hemispheric and global records. The possibility that the trees are responding directly to CO2 fertilisation is explored, using a high-precision record of CO2, obtained from air in Antarctic ice and firn, plus direct measurements of air from Cape Grim. The temperature forcing appears capable of explaining the ring-width variations in the alpine trees over the full range of observed periods, whereas CO2 fertilisation would require a more complex interaction and is not supported by other arguments. Two millennia-long tree-ring reconstructions of summer temperatures from South America do not exhibit the recent warming, nor other features found in the Tasmanian record on decadal to century time-scales. In fact, the South American chronologies bear little resemblance to each other, but do, however, reflect their own regional instrumental records. The Mt Read ring-width chronology, and the instrumental temperature series used for its calibration, also co-vary with climate influences of a distinctly regional character, yet still replicate many of the features reported as hemispheric and global temperatures over the last century. Spectral analysis of the Mt Read tree-ring data over the full 2792 years suggests that at least part of the recent warming in the instrumental records could be a consequence of "natural forcing" of the record, complicating an interpretation in terms of a greenhouse-forced warming

Two wrongs make a right: Addressing underreporting in binary data from multiple sources

© The Author(s) 2017. Media-based event data-i.e., data comprised from reporting by media outlets-are widely used in political science research. However, events of interest (e.g., strikes, protests, conflict) are often underreportedby these primary and secondary sources, producing incomplete data that risks inconsistency and bias in subsequent analysis. While general strategies exist to help ameliorate this bias, these methods do not make full use of the information often available to researchers. Specifically, much of the event data used in the social sciences is drawn from multiple, overlapping news sources (e.g., Agence France-Presse, Reuters). Therefore, we propose a novel maximum likelihood estimator that corrects for misclassification in data arising from multiple sources. In the most general formulation of our estimator, researchers can specify separate sets of predictors for the true-event model and each of the misclassification models characterizing whether a source fails to report on an event. As such, researchers are able to accurately test theories on both the causes of and reporting on an event of interest. Simulations evidence that our technique regularly outperforms current strategies that either neglect misclassification, the unique features of the data-generating process, or both. We also illustrate the utility of this method with a model of repression using the Social Conflict in Africa Database

Second-order estimating equations for clustered current status data from family studies using response-dependent sampling

Studies about the genetic basis for disease are routinely conducted through family studies under response-dependent sampling in which affected individuals called probands are sampled from a disease registry, and their respective family members (non-probands) are recruited for study. The extent to which the dependence in some feature of the disease process (e.g. presence, age of onset, severity) varies according to the kinship of individuals, reflects the evidence of a genetic cause for disease. When the probands are selected from a disease registry it is common for them to provide quite detailed information regarding their disease history, but non-probands often simply provide their disease status at the time of contact. We develop conditional second-order estimating equations for studying the nature and extent of within-family dependence which recognizes the biased sampling scheme employed in family studies and the current status data provided by the non-probands. Simulation studies are carried out to evaluate the finite sample performance of different estimating functions and to quantify the empirical relative effciency of the various methods. Sensitivity to model misspecification is also explored. An application to a motivating psoriatic arthritis family study is given for illustration.The authors thank Drs. Dafna Gladman, Vinod Chandran and Lihi Eder for stimulating collaboration and helpful discussions involving the psoriatic arthritis research program. This research was nancially supported by grants from the UK Medical Research Council [Unit programme no. MC UP 1302/3], the Natural Sciences and Engineer- ing Research Council of Canada (RGPIN 155849) and the Canadian Institutes for Health Research (FRN 13887). Richard Cook is a Tier I Canada Research Chair in Statistical Methods for Health Research

Evaluating Matrix Circuits

The circuit evaluation problem (also known as the compressed word problem) for finitely generated linear groups is studied. The best upper bound for this problem is $\mathsf{coRP}$, which is shown by a reduction to polynomial identity testing. Conversely, the compressed word problem for the linear group $\mathsf{SL}_3(\mathbb{Z})$ is equivalent to polynomial identity testing. In the paper, it is shown that the compressed word problem for every finitely generated nilpotent group is in $\mathsf{DET} \subseteq \mathsf{NC}^2$. Within the larger class of polycyclic groups we find examples where the compressed word problem is at least as hard as polynomial identity testing for skew arithmetic circuits

Identification of liver metastases with probe-based confocal laser endomicroscopy at two excitation wavelengths.

BACKGROUND: Metastasis of colorectal cancer to the liver is the most common indication for hepatic resection in a western population. Incomplete excision of malignancy due to residual microscopic disease normally results in worse patient outcome. Therefore, a method aiding in the real time discrimination of normal and malignant tissue on a microscopic level would be of benefit. MATERIAL AND METHODS: The ability of fluorescent probe-based confocal laser endomicroscopy (pCLE) to identify normal and malignant liver tissue was evaluated in an orthotopic murine model of colorectal cancer liver metastasis (CRLM). To maximise information yield, two clinical fluorophores, fluorescein and indocyanine green (ICG) were injected and imaged in a dual wavelength approach (488 and 660 nm, respectively). Visual tissue characteristics on pCLE examination were compared with histological features. Fluorescence intensity in both tissues was statistically analysed to elucidate if this can be used to differentiate between normal and malignant tissue. RESULTS: Fluorescein (488 nm) enabled good visualisation of normal and CRLM tissue, whereas ICG (660 nm) visualisation was limited to normal liver tissue only. Fluorescence intensity in areas of CRLM was typically 53-100% lower than normal hepatic parenchyma. Using general linear mixed modelling and receiver operating characteristic analysis, high fluorescence intensity was found to be statistically more likely in normal hepatic tissue. CONCLUSION: Real time discrimination between normal liver parenchyma and metastatic tissue with pCLE examination of fluorescein and ICG is feasible. Employing two (rather than a single) fluorophores allows a combination of qualitative and quantitative characteristics to be used to distinguish between hepatic parenchyma and CRLM. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

iSchools and archival studies

Whispers and rumors about the iSchool movement lead some to fear that this represents yet another shift away from the valued traditions of library schools, threatening something far different than what library science pioneers ever envisioned. Predating the iSchool movement, however, were other programmatic shifts such as those that led to the formalization of graduate archival education. This essay argues that such evolution is essential to our future, as iSchools tackle the increasingly complex issues confronting a digital society. We consider the mission and history of iSchools and of archival studies, the basic elements and concepts of archival studies that are critical to iSchools, and the relationship between iSchools and the changing nature of personal and institutional archives. © 2009 Springer Science+Business Media B.V