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To my astonishment, I find myself not "old," not as we all feel at least for moments during middle age, but really old: eighty-seven-years-plus as I write this piece. It won't be finished until I am eighty-eight! That hard-to-swallow fact is what allows me this rather self-indulgent retrospective on a Victorianist career that has spanned several generations of criticism and scholarship. Perhaps, I dare to think, a look back at the arc of that career might be of interest to someone beside myself, moving as it does from the time—around Christmas 1958, when I began writing on a portable electric typewriter a dissertation on George Eliot and determinism—to this moment, when writing a dissertation on a single author seems rather risky and professionally unhelpful, especially if one tries to do it on a typewriter. [ABSTRACT FROM AUTHOR]

Summary: Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low‐grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome‐wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10−5, P = 5.91 × 10−6, P = 4.91 × 10−5, P = 6.46 × 10−5). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10−5). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU. [ABSTRACT FROM AUTHOR]

Suggests that William Hale White's (Mark Rutherford) admiration for Charlotte Bronte may have led to imitation, as seen from chapter 9 of `Clara Hopgood' and chapter 23 of `Jane Eyre.' Letter cited as showing White's esteem for Bronte; Key passages in the two chapters discussed.

Looks at a passage in `The Revolution in Tanner's Lane,' where Mark Rutherford displays his radicalism, when discussing his hero Zachariah's attempts to get work and Carlyle's `French Revolution.' Passage outlined; Verse in which Rutherford claims authority of experience.

Presents an attempt to date the action of Mark Rutherford's `Clara Hopgood.' Rationale behind the care with which Rutherford dated `Clara Hopgood'; Key events that have been dated in the story; Relevance of Rutherford's account in `The Autobiography' of the effect of Wordsworth's `Lyrical Ballads' on him.

Background: Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC).Methods: One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate.Results: Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024-1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007-1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS.Conclusion: Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test. [ABSTRACT FROM AUTHOR]

The article titled "A word of heartfelt thanks to our reviewers" expresses gratitude to the scientists who served as reviewers for volume 45 of BioEssays. The editorial staff acknowledges their dedication, knowledge, and cooperation in providing thoughtful reviews in a timely manner. The list of reviewers includes a diverse range of scientists from various backgrounds and fields of expertise. [Extracted from the article]

A list of the editorial consultants for the journal is presented, that includes Julie Aarestrup, Mohamed Abbas and Michal Abrahamowicz.

Ultraviolet radiation (UVR) is a strong and ubiquitous risk factor for cutaneous melanoma, emitted naturally by the sun but also artificial sources. To shed light on the potential impact of interventions seeking to reduce exposure to UVR in both high and low risk populations, we quantified the number of cutaneous melanomas attributable to UVR worldwide. Population attributable fractions and numbers of new melanoma cases in adults due to ambient UVR were calculated by age and sex for 153 countries by comparing the current melanoma burden with historical data, i.e., the melanoma burden observed in a population with minimal exposure to UVR. Secondary analyses were performed using contemporary melanoma incidence rates in dark‐skinned African populations with low UVR susceptibility as reference. Globally, an estimated 168,000 new melanoma cases were attributable to excess UVR in 2012, corresponding to 75.7% of all new melanoma cases and 1.2% of all new cancer cases. This burden was concentrated in very highly developed countries with 149,000 attributable cases and was most pronounced in Oceania, where 96% of all melanomas (representing 9.3% of the total cancer burden) were attributable to excess UVR. There would be approximately 151,000 fewer melanoma cases worldwide were incidence rates in every population equivalent to those observed in selected low‐risk (dark‐skinned, heavily pigmented) reference populations. These findings underline the need for public health action, an increasing awareness of melanoma and its risk factors, and the need to promote changes in behavior that decrease sun exposure at all ages. [ABSTRACT FROM AUTHOR]

First published in England under the title Illumination, Harold Frederic's novel The Damnation of Theron Ware has long been considered in terms of its Americanness. Frederic's 1896 portrayal of a small-town Methodist minister in upstate New York has been praised for its authentic regional depiction, as well as its engagement with changing national demographics and portrayal of the American Methodist church. Yet Illumination1 s place in the tradition of British clerical novels has largely been overlooked. In addition to dramatizing the character and calling of the clergyman, clerical novels addressed the social place of the minister and the obligations of the profession in nations that considered themselves to be Christian. Congregational expectations, financial strain, personal ambition, and crises of belief all impact the effective ministry of the clergyman in these novels. This essay expands the critical emphasis which has tended to see Frederic's novel as particularly American, placing Illumination in context with novels by Trollope, Oliphant, Barrie, and others, as well as in context with authors of 19th century ministerial handbooks. In so doing, it calls for a heightened appreciation of the complexity and achievement of Frederic's best-known work. [ABSTRACT FROM AUTHOR]

We describe the clinicopathologic findings, relative prevalence, and pathogens associated with infectious keratoconjunctivitis in mule deer (Odocoileus hemionus) in Wyoming. Seventeen cases with ocular lesions were identified among 1,036 mule deer postmortem submissions (1.6%) in an ~16 y period. Sixteen cases were observed in winter and most were in male (15 cases) and juvenile (13 cases) deer. Blindness was the most commonly reported clinical sign (10 cases). A herpesvirus was detected only in the 4 cases of bilateral necrotizing bulbar conjunctivitis. Phylogenetic analysis of glycoprotein amino acid sequences consistently identified this virus as a novel alphaherpesvirus. In 2 of these herpesvirus-positive cases, Actinomyces sp. and Moraxella ovis were also identified. Trueperella pyogenes was identified in 4 cases of unilateral ulcerative keratitis, keratoconjunctivitis, and panophthalmitis. M. ovis was cultured from 3 cases of bilateral conjunctivitis and keratoconjunctivitis. In the remaining cases, isolates included Moraxella bovis (1 case), Staphylococcus sp. and Streptococcus sp. (2), Flavobacterium sp. and Pseudomonas sp. (2), Escherichia coli and Enterobacter sp. (1), and bovine viral diarrhea virus 1 (1). No pathogens were identified in 2 cases. The relative prevalence of keratoconjunctivitis in mule deer in Wyoming appears to be low, and this disease is most commonly associated with infection by a novel alphaherpesvirus, T. pyogenes, and M. ovis. [ABSTRACT FROM AUTHOR]

Ca2+ influx triggers the release of synaptic vesicles at the presynaptic active zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is critical for understanding synaptic transmission. However, this has remained challenging to establish at the required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy to quantify the number (20–330) and arrangement (mostly linear 70 nm × 100–600 nm clusters) of Ca2+ channels at AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we analyze presynaptic Ca2+ signals at the nanometer scale and find confined elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence lifetime analysis, we arrive at estimates of the Ca2+ concentrations at stimulated IHC AZs of on average 25 µM. We propose that IHCs form bassoon-dependent presynaptic Ca2+-channel clusters of similar density but scalable length, thereby varying the number of Ca2+ channels amongst individual AZs. [ABSTRACT FROM AUTHOR]

In a competing risks analysis, interest lies in the cause-specific cumulative incidence function (CIF) that can be calculated by either (1) transforming on the cause-specific hazard or (2) through its direct relationship with the subdistribution hazard. We expand on current competing risks methodology from within the flexible parametric survival modelling framework (FPM) and focus on approach (2). This models all cause-specific CIFs simultaneously and is more useful when we look to questions on prognosis. We also extend cure models using a similar approach described by Andersson et al for flexible parametric relative survival models. Using SEER public use colorectal data, we compare and contrast our approach with standard methods such as the Fine & Gray model and show that many useful out-of-sample predictions can be made after modelling the cause-specific CIFs using an FPM approach. Alternative link functions may also be incorporated such as the logit link. Models can also be easily extended for time-dependent effects. [ABSTRACT FROM AUTHOR]

In competing-risks analysis, the cause-specific cumulative incidence function (CIF) is usually obtained in a modeling framework by either 1) transforming on all cause-specific hazards or 2) transforming by using a direct relationship with the subdistribution hazard function. We expand on current competing-risks methodology from within the flexible parametric survival modeling framework and focus on the second approach. This approach models all cause-specific CIFs simultaneously and is more useful for answering prognostic-related questions. We propose the direct flexible parametric survival modeling approach for the cause-specific CIF. This approach models the (log cumulative) baseline hazard without requiring numerical integration, which leads to benefits in computational time. It is also easy to make out-of-sample predictions to estimate more useful measures and incorporate alternative link functions, for example, logit links. To implement these methods, we introduce a new estimation command, stpm2cr, and demonstrate useful predictions from the model through an illustrative melanoma dataset. [ABSTRACT FROM AUTHOR]

The article offers information on author, and poet George MacDonald. It mentions about an account of his work such as books "Alec Forbes of Howglen," "A Seaboard Parish," and "Wilfrid Cumbermede"; and an account of books written by his son such as "George Macdonald and his wife," and "Jack and Jill: A Fairy Story."

Presents correspondence on literature. Attempts to a critical edition of Mark Rutherford fictions of W. Hale White; Status of Walt Whitman as father of American poetry; Criticisms in the representation of the essay the Other.

The article lists the journal's editorial consultants as of December 2022, including Linda S. Adair, Jennifer Ahern, and Tarik Benmarhnia.