Vulvar cancer : patterns of recurrence, quality of life and extended indications for the sentinel node technique

Background: Vulvar cancer is a rare malignancy and few studies have addressed the course of disease and the impact of physical and psychological symptoms on healthrelated quality of life (HRQOL) over time. In addition, extending the indication for sentinel node biopsy in vulvar cancer requires further evaluation. The overall aim of this thesis was to investigate patterns of recurrence and the trajectory of symptoms and HRQOL in a nationwide population of women with vulvar cancer, and to examine the feasibility of sentinel node biopsy in larger and multifocal tumours. Methods: Study I included all women diagnosed with primary vulvar squamous cell carcinoma (VSCC) from 2012-2015 whose health data were recorded in the Swedish Quality Registry for Gynaecologic Cancer (n=489). The cumulative incidences and survival rates for local, groin, and distant recurrences were calculated. In addition, the potential impact of not performing surgical groin staging on survival was assessed. In Studies II and III the relationship between physical and psychological symptoms and HRQOL in a nationwide longitudinal cohort of women with primary vulvar cancer diagnosed from 2019-2021 (n=153) were examined utilizing validated questionnaires (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30, the EORTC-QLQ VU34, the Supportive Care Needs Survey, and the Hospital Anxiety and Depression Scale). Anxiety, depression, local vulvar and lymphoedema symptoms and their impact on HRQOL were investigated at the time of diagnosis, as well as 3 and 12 months after treatment. Study IV was a nationwide prospective, single-arm interventional pilot study. Women with VSCC and tumours ≥ 4 cm in diameter (Group 1), multifocal tumours (Group 2) or a first local recurrence (Groups 3 and 4) diagnosed between 2019-2022 (total n=64) underwent sentinel node biopsy in addition to standard inguinofemoral lymphadenectomy. Detection rates and negative predictive values were calculated. Results: In Study I after a median follow-up of 52 months, the recurrence rate was 22.3% (vulva 61%, groin 30%, and distant 9%). Groin and distant recurrences occurred primarily within the first two years after treatment, while the incidence of local recurrences increased continuously during follow-up. The median two-year post-recurrence overall survival was 57.8% for vulvar, 17.2% for groin, and 0% for distant recurrences. Omission of surgical groin staging in 23.7% of the patients with presumed stage IB-II disease was associated with poorer survival. In Studies II and III 140 (92%) of the women completed at least one questionnaire and 105 (69%) completed all three. At the time of diagnosis, 41.8% of the women reported elevated anxiety, a proportion that declined to 29.5% 12 months after treatment. Insomnia, a high need for information and persistent vulvar symptoms were associated with enhanced anxiety. Vulvar symptoms were associated with impaired HRQOL and improved after treatment, whereas symptoms of leg lymphoedema became more common after treatment. Emotional, role, cognitive, and social functioning, as well as global and mental health became better following treatment. In Study IV, the detection rates in Groups 1 and 2 were 94.1–100% per patient and 84.1–85.3% per groin, respectively. There were no false-negative sentinel nodes, i.e., the negative predictive value was 100% (95% CI 91.2%-100% for Group 1 and 83.9%-100% for Group 2). Conclusions: Local recurrences are common in patients with vulvar cancer, with a stable incidence throughout the period of surveillance. Lack of surgical groin staging is associated with poorer survival. Women with primary vulvar cancer report a high prevalence of vulvar symptoms, anxiety, and impaired HRQOL at the time of diagnosis. Alleviating vulvar symptoms, insomnia, and unmet needs for information might reduce anxiety. Extending the application of sentinel node biopsy to women with tumours ≥ 4 cm in diameter, as well as to those with multifocal tumours seems feasible

Evaluation of Juntos 4-H: A Wraparound Program Helping Latinx High Schoolers Succeed

Preprogram and postprogram surveys of 241 Latinx 4-H youths from five counties in North Carolina provided a snapshot of their experiences in the Juntos 4-H program. The study findings demonstrate that Juntos 4-H has positive impacts on academics, college readiness, parent engagement, and community engagement. Suggestions are made to help Extension professionals elsewhere develop effective programs for Latinx youths

The Holes in the cheese : improving engineering students' generic communicative competencies

Engineers spend considerable time communicating technical details to various audiences. This requires communicative competence which is linked to the underlying knowledge and skills in the engineering disciplines. The metaphor 'holes in the cheese‘ is used to describe a particular group of reading and writing competencies which are not yet adequately developed in students, but which are expected to be in place at their educational level, and which are further characterised as follows: (a) while it is reasonable to include limited revision of prior topics or competencies in a mainstream programme, substantive interventions to address them must be extra-curricular; (b) a significant proportion of students require development in this regard; (c) they are seldom explicitly taught; (d) most engineering academics are not explicitly trained to identify or address them; (e) identifying and addressing them through traditional assessment of written work ('red ink‘) is time-consuming for academics; (f) moreover, addressing them through traditional assessment is seldom successful: while the document may have been corrected, an improvement in competence is seldom established by this method. By way of evidence, this paper attempts to name, explain and illustrate these 'holes in the cheese‘ in terms that are sufficiently explicit and concrete so that fellow engineering academics can readily understand and relate to them. This evidence is illustrative and anecdotal, serving as a point of discussion rather than a conclusion of fact. With regard to reading fluency and comprehension, the reading speeds of students on intake to supplementary interventions, over a three year period, have typically been below the reading speeds regarded as a lower threshold for university students when reading fiction and non-technical materials. With regard to writing, typical challenges include grammatical errors as well as structure, organisation, logic, and integration / synthesis of information from multiple sources

A less-traveled path for data in bioprocess development: From dynamic experiments to dynamic process models

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The invasion history, distribution and colour pattern forms of the harlequin ladybird beetle Harmonia axyridis (Pall.) (Coleoptera, Coccinellidae) in Slovakia, Central Europe

The harlequin ladybird beetle Harmonia axyridis (Coleoptera, Coccinellidae) has invaded and established in Slovakia. Following unintentional introduction in 2008, the spread of the alien coccinellid was very fast. By the end of 2009, it was recorded across the whole country, and by the end of 2012 it was widely distributed and common in various habitats, particularly gardens, orchards and urban areas, where it was most frequent on trees. The rate of eastward spread was approximately 200 km year-1, similar to the overall rate of spread in Europe. Between 2008 and 2012, the coccinellid was recorded in a total of 153 localities, in altitudes ranging from 98 to 1, 250 m. Most records of this species were made in lowlands, hilly areas and valleys separating mountain ridges. However, it was only rarely documented in areas above 700 m a.s.l. The non-melanic colour form (f. succinea) was dominant along a longitudinal transect including eight urban areas across Slovakia, with the frequency of melanic forms (f. spectabilis and f. conspicua together) between 6.3 and 19.2% and a median equal to 10.5%. The invasion history and distribution of H. axyridis in Slovakia are discussed with regard to the time sequence of records, rate of spread, altitudinal distribution, anthropogenic dispersal, effective recording, proportion of melanic forms and other relevant aspects associated with the spread of this successful invader

Epsilon*: Privacy Metric for Machine Learning Models

We introduce Epsilon*, a new privacy metric for measuring the privacy risk of a single model instance prior to, during, or after deployment of privacy mitigation strategies. The metric does not require access to the training data sampling or model training algorithm. Epsilon* is a function of true positive and false positive rates in a hypothesis test used by an adversary in a membership inference attack. We distinguish between quantifying the privacy loss of a trained model instance and quantifying the privacy loss of the training mechanism which produces this model instance. Existing approaches in the privacy auditing literature provide lower bounds for the latter, while our metric provides a lower bound for the former by relying on an (${\epsilon}$,${\delta}$)-type of quantification of the privacy of the trained model instance. We establish a relationship between these lower bounds and show how to implement Epsilon* to avoid numerical and noise amplification instability. We further show in experiments on benchmark public data sets that Epsilon* is sensitive to privacy risk mitigation by training with differential privacy (DP), where the value of Epsilon* is reduced by up to 800% compared to the Epsilon* values of non-DP trained baseline models. This metric allows privacy auditors to be independent of model owners, and enables all decision-makers to visualize the privacy-utility landscape to make informed decisions regarding the trade-offs between model privacy and utility

Preferably Plinian and Pumaceous: Implications of Microbial Activity in Modern Volcanic Deposits at Askja Volcano, Iceland, and Relevancy for Mars Exploration

To search more efficiently for a record of past life on Mars, it is critical to know where to look and thus maximize the likelihood of success. Large-scale site selection for the Mars 2020 mission has been completed, but small (meter to 10 cm)-scale relationships of microenvironments will not be known until the rover reaches the surface. Over a 2 m transect at a modern volcanic deposit on the flank of Askja volcano in the barren highlands of Iceland, we compared two biological indicators (ATP activity and 16SrRNA amplicon sequence composition) to physical characteristics including bulk chemical composition, spectral signatures of mineralogy, and grain size. Using analytical instrumentation analogous to those available on Mars rovers, we were able to characterize the geological setting of the deposits and link physical parameters to microbial abundance and diversity. In general, methanogenesis, methanotrophy/methylotrophy, and nitrate reduction were the functional traits most associated with microbial community shift along the transect. Core microbiome members tended to be associated with nitrate reduction, and relative abundance of core microbes was strongly related to free water in the deposit. Community compositional shift of the rare microbiome was related to microenvironmental changes such as change in grain size, geochemistry, and age of deposit. These correlations lead us to suggest a sampling strategy that accounts for Martian geology, looking for undisturbed (not remobilized) explosive volcanic ash below pumice that could maximize diversity and abundance of different bioindicators. Our study also illustrates the importance of studying the variability across microenvironments in low biomass settings on earth

The Science Case for an Extended Spitzer Mission

Although the final observations of the Spitzer Warm Mission are currently scheduled for March 2019, it can continue operations through the end of the decade with no loss of photometric precision. As we will show, there is a strong science case for extending the current Warm Mission to December 2020. Spitzer has already made major impacts in the fields of exoplanets (including microlensing events), characterizing near Earth objects, enhancing our knowledge of nearby stars and brown dwarfs, understanding the properties and structure of our Milky Way galaxy, and deep wide-field extragalactic surveys to study galaxy birth and evolution. By extending Spitzer through 2020, it can continue to make ground-breaking discoveries in those fields, and provide crucial support to the NASA flagship missions JWST and WFIRST, as well as the upcoming TESS mission, and it will complement ground-based observations by LSST and the new large telescopes of the next decade. This scientific program addresses NASA's Science Mission Directive's objectives in astrophysics, which include discovering how the universe works, exploring how it began and evolved, and searching for life on planets around other stars.Comment: 75 pages. See page 3 for Table of Contents and page 4 for Executive Summar