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This study surveyed the members of a professional library organization for their perceptions of their online librarianship role. In particular, the survey sought to examine any change in online librarianship roles after March 2020 as a result of the COVID-19 pandemic lockdowns. Participants were administered a survey comprised of both quantitative and qualitative response options. Findings present a nuanced professional environment post-lockdown in which individual job duties largely remained the same; however participants reported increased demands stemming from workplace issues, including attrition and lack of resources.

International audience; Abstract. The mid-17th century is characterized by a cluster of explosive volcanic eruptions in the 1630s and 1640s, climatic conditions culminating in the Maunder Minimum, and political instability and famine in regions of western and northern Europe as well as China and Japan. This contribution investigates the sources of the eruptions of the 1630s and 1640s and their possible impact on contemporary climate using ice core, tree-ring, and historical evidence but will also look into the socio-political context in which they occurred and the human responses they may have triggered. Three distinct sulfur peaks are found in the Greenland ice core record in 1637, 1641–1642, and 1646. In Antarctica, only one unambiguous sulfate spike is recorded, peaking in 1642. The resulting bipolar sulfur peak in 1641–1642 can likely be ascribed to the eruption of Mount Parker (6∘ N, Philippines) on 26 December 1640, but sulfate emitted from Komaga-take (42∘ N, Japan) volcano on 31 July 1641 has potentially also contributed to the sulfate concentrations observed in Greenland at this time. The smaller peaks in 1637 and 1646 can be potentially attributed to the eruptions of Hekla (63∘ N, Iceland) and Shiveluch (56∘ N, Russia), respectively. To date, however, none of the candidate volcanoes for the mid-17th century sulfate peaks have been confirmed with tephra preserved in ice cores. Tree-ring and written sources point to cold conditions in the late 1630s and early 1640s in various parts of Europe and to poor harvests. Yet the early 17th century was also characterized by widespread warfare across Europe – and in particular the Thirty Years' War (1618–1648) – rendering any attribution of socio-economic crisis to volcanism challenging. In China and Japan, historical sources point to extreme droughts and famines starting in 1638 (China) and 1640 (Japan), thereby preceding the eruptions of Komaga-take (31 July 1640) and Mount Parker (4 January 1641). The case of the eruption cluster between 1637 and 1646 and the climatic and societal conditions recorded in its aftermath thus offer a textbook example of difficulties in (i) unambiguously distinguishing volcanically induced cooling, wetting, or drying from natural climate variability and (ii) attributing political instability, harvest failure, and famines solely to volcanic climatic impacts. This example shows that while the impacts of past volcanism must always be studied within the contemporary socio-economic contexts, it is also time to move past reductive framings and sometimes reactionary oppositional stances in which climate (and environment more broadly) either is or is not deemed an important contributor to major historical events.

Paediatric-type diffuse high-grade gliomas are classified into distinct subgroups based upon their location and defining molecular alterations, with very poor clinical outcomes in patients >3yrs. This extensive inter-tumour heterogeneity is further complicated by a wide diversity of genotypically- and phenotypically-distinct subclonal populations within individual tumours, providing a substantial barrier to developing effective treatments. We have sought to understand the dynamic cellular make-up of PDHGGs such that novel strategies aimed at targeting specific subpopulations based upon their contribution to disease progression as whole may be employed. Two complementary approaches have been undertaken to address this – first by carrying out single-cell profiling of bulk specimens, and the second isolation and propagation of single-cell-derived stem cell-like cultures in vitro. To-date we have studied 10 cases and a total of 218 subclonal colonies from both DMG-H3K27 and DHG-WT. In a spinal metastatic case of DMG-H3K27, lpWGS-FISH highlighted subpopulations driven by mis-segregation of amplified oncogenic ecDNA, and mutually exclusive subpopulations defined by MYCN, PDGFRA and CCND1. Through integrated analysis of scRNA-seq and scATAC-seq, we show distinct chromatin accessibility profiles to underlie gene expression signatures defining unique subpopulations of cells. In addition to cycling populations and those associated with lineage-specificity, we identified ‘aggressive’ subpopulations defined by significant upregulation of immediate early response genes such as FOS/FOSL1/JUN, those associated with promotion of invasion-migration such as SERPINs and MMPs. These subpopulations could be mapped to isolated single-cell-derived subclones with highly proliferative or motile phenotypes, defined by comprehensive profiling of expressed and secreted proteins. Differential cis-regulation driving cell identity-tumorigenesis was found in one example to occur via a trans-histone mechanism mediated by an H4-lysine-methyltransferase, KMT5B. Application of functionally-defined interventional strategies aimed at disrupting the interactions between these subpopulations based upon evolutionary biology principles may offer a novel approach to treat these otherwise incurable tumours in children and young adults.

BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 10.4 months (8.8-14.4) (p

Historical precipitation records are fundamental for the management of water resources, yet rainfall observations typically span 100–150 years at most, with considerable uncertainties surrounding earlier records. Here, we analyse some of the longest available precipitation records globally, for England and Wales, Scotland and Ireland. To assess the credibility of these records and extend them further back in time, we statistically reconstruct (using independent predictors) monthly precipitation series representing these regions for the period 1748–2000. By applying the Standardized Precipitation Index at 12‐month accumulations (SPI‐12) to the observed and our reconstructed series we re‐evaluate historical meteorological droughts. We find strong agreement between observed and reconstructed drought chronologies in post‐1870 records, but divergence in earlier series due to biases in early precipitation observations. Hence, the 1800s decade was less drought prone in our reconstructions relative to observations. Overall, the drought of 1834–1836 was the most intense SPI‐12 event in our reconstruction for England and Wales. Newspaper accounts and documentary sources confirm the extent of impacts across England in particular. We also identify a major, “forgotten” drought in 1765–1768 that affected the British‐Irish Isles. This was the most intense event in our reconstructions for Ireland and Scotland, and ranks first for accumulated deficits across all three regional series. Moreover, the 1765–1768 event was also the most extreme multi‐year drought across all regional series when considering 36‐month accumulations (SPI‐36). Newspaper and other sources confirm the occurrence and major socio‐economic impact of this drought, such as major rivers like the Shannon being fordable by foot. Our results provide new insights into historical droughts across the British Irish Isles. Given the importance of historical droughts for stress‐testing the resilience of water resources, drought plans and supply systems, the forgotten drought of 1765–1768 offers perhaps the most extreme benchmark scenario in more than 250‐years., We reconstruct and re‐evaluate historical droughts across the British Irish Isles (England and Wales, Scotland and Ireland) since 1748 and identify a major, “forgotten” drought in 1765–1768. We show that the event was likely the most extreme multi‐year drought across the region. Newspaper and other sources confirm the occurrence and major socio‐economic impact of this drought, which offers perhaps the most extreme benchmark scenario in more than 250‐years for stress‐testing drought and water resource plans.

Frontotemporal lobar degeneration (FTLD) consists of a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders that chiefly affect frontal and temporal lobes. Clinical presentation in FTLD includes behavioural variant frontotemporal dementia, progressive nonfluent aphasia and semantic dementia (SD). Pathologically, FTLD is subdivided based on accumulation of abnormal intracellular proteins including transactivation response DNA-binding protein 43 kDa (TDP-43) [1, 2]. TDP-43 pathology in FTLD is classified into five pathological subgroups depending on its morphological features: TDP-43 type A, B, C, D and E [2, 3].

Paediatric-type diffuse high-grade gliomas are classified into distinct subgroups based upon their location and defining molecular alterations, with very poor clinical outcomes in patients >3yrs. This extensive inter-tumour heterogeneity is further complicated by a wide diversity of genotypically- and phenotypically-distinct subclonal populations within individual tumours, providing a substantial barrier to developing effective treatments. We aimed to understand the dynamic cellular make-up of PDHGGs such that novel strategies aimed at targeting specific subpopulations based upon their contribution to disease progression as whole may be employed. Two complementary approaches have been undertaken to address this – first by carrying out single-cell profiling of bulk specimens, and the second isolation and propagation of single-cell-derived stem cell-like cultures in vitro. To-date we have studied 10 cases and a total of 218 subclonal colonies from both DMG-H3K27 and DHG-WT. In a spinal metastatic case of DMG-H3K27, lpWGS/FISH highlighted subpopulations driven by mis-segregation of amplified oncogenic ecDNA, and mutually exclusive subpopulations defined by MYCN, PDGFRA and CCND1. Through integrated analysis of scRNA-seq and scATAC-seq, we show distinct chromatin accessibility profiles to underlie gene expression signatures defining unique subpopulations of cells. In addition to cycling populations and those associated with lineage-specificity, we identified ‘aggressive’ subpopulations defined by significant upregulation of immediate early response genes such as FOS/FOSL1/JUN, those associated with promotion of invasion/migration such as SERPINs and MMPs. These subpopulations could be mapped to isolated single-cell-derived subclones with highly proliferative and/or motile phenotypes, defined by comprehensive profiling of expressed and secreted proteins. Differential cis-regulation driving cell identity/tumorigenesis was found in one example to occur via a trans-histone mechanism mediated by an H4-lysine-methyltransferase, KMT5B. Application of functionally-defined interventional strategies aimed at disrupting the interactions between these subpopulations based upon evolutionary biology principles may offer a novel approach to treat these otherwise incurable tumours in children and young adults.

PDHGG are a diverse group of childhood brain tumours comprising multiple subgroups carrying distinct molecular drivers. Patient-derived models accurately recapitulating this underlying biology are critical for mechanistic/preclinical studies aimed at improving patient outcome, however their behaviour over time in the environments in which they are propagated, and how this relates to the human disease, is largely unknown. To explore this, we collected 94 models of PDHGG established as 2D/3D stem cell cultures in vitro, and generated patient-derived xenografts (PDX) in 33/62 specimens implanted orthotopically in vivo. We carried out exome/targeted sequencing, methylation profiling and RNAseq to profile cells through their first 25 passages in culture, and sequential implantation from p0-p2 in mice. In 15/83 cultures, we observed enrichment of gene expression signatures of non-malignant cells over the first 5 passages, with concurrent depletion of somatic mutations/CNAs, excluding them from further study. Validated models retained tumour-matched genotypes, CNAs and driver alterations including H3.3G34R, H3.3/H3.1K27M, BRAF and ACVR1 over time, however subclonal alterations underwent selection in culture which profoundly altered their response to targeted drug treatment. In 6/7 PDGFRA-mutant models, activating mutations were selected against between p5-20 in 2D and/or 3D, whilst MAPK pathway mutations in NF1/PIK3R1 similarly diverged over 15 passages under different growth conditions, resulting in isogenic models with differential signalling, in vivo tumorigenicity, and in vitro sensitivity to multiple MEK inhibitors. In PDXs, serial xenografting reduced the time to tumour formation by up to half, with a concomitant shift in clonal architecture. Multi-region sequencing of diffusely-infiltrating tumours showed selection for alterations such as PIK3CA/NF1 at distant sites, with evidence for convergent evolution of subclonal mutations, as in human tumours. Understanding the evolutionary dynamics of targetable/predictive alterations in PDHGG model systems is key to developing new and effective therapeutic interventions in this highly heterogenous disease.

Scholarly publishing continues to be a prominent expectation for many academic librarians. This survey explores characteristics, behaviors, motivations, institutional supports, and educational opportunities that help library practitioners become successful authors. It also looks at perceived confidence in research skills of both novice and experienced librarians. Many librarians show confidence in research activities related to their overall job assignments (literature searching, writing, and such) but find more sophisticated research skills, such as statistical analysis, more challenging. Findings indicate that having additional graduate research experience beyond the library degree, time-management skills, and collaboration with other researchers may provide useful benefits.

Large-scale 3D histology reconstruction of the human brain with MRI as volumetric reference generally requires reassembling the tissue blocks into the MRI space, prior to any further reconstruction of the histology of the individual blocks. This is a challenging registration problem, particularly in the frequent case that blockface photographs of paraffin embedded tissue are used as intermediate modality, as their contrast between white and gray matter is rather low. Here we propose a registration framework to address this problem, relying on two key components. First, blocks are simultaneously aligned to the MRI while exploiting the spatial constraints that they impose on each other, by means of a customized soft shape constraint (similarly to a jigsaw puzzle). And second, we adopt a hierarchical optimization strategy that capitalizes on our prior knowledge on the slicing and blocking procedure. Our framework is validated quantitatively on synthetic data, and qualitatively on the histology of a whole human hemisphere.

Phenylalkyl isoselenocyanate (ISC) compounds were recently designed in our laboratory by incorporating the anticancer element selenium into a panel of phenylalkyl isothiocyanates (ITCs), known to have anticancer properties. A structural activity investigation was carried out to compare the ISC and ITC panels. Cell viability assay and Annexin V staining for apoptosis showed ISC compounds to be more potent in killing A549 lung adenocarcinoma cells. Both ITCs and ISCs were able to deplete reduced glutathione (GSH) in cells, ISCs more rapidly, but ITCs to a greater extent. ISC compounds had a higher rate of reaction to thiol (–SH) groups as determined by pseudo first order kinetics than the corresponding carbon chain length ITC. The equilibrium concentrations of the GSH and protein thiol conjugates did not differ significantly when comparing sulfur to selenium compounds of the same carbon chain length, and did follow the same trend of displaying decreasing reactivity with increasing carbon chain length for both ITCs and ISCs. Furthermore, only ITCs were able to induce cell cycle arrest, suggesting that protein targets inside the cell may differ for the S and Se panels. Finally, the panels were tested for their ability to redox cycle when reacted with GSH to form superoxide and other reactive oxygen species (ROS). ISC compounds showed a much greater ability to redox cycle than corresponding ITCs, and were able to induce higher levels of ROS in A549 cells. Also, the direct pro-apoptotic effects of ISCs and ITCs were inhibited by GSH and potentiated by depletion of intracellular GSH by buthionine sulfoximine. In conclusion, our studies suggest that the redox-cycling capabilities of ISCs and thus generation of higher levels of ROS may be contributing to the increased cytotoxicity of ISC compounds in A549 cells, compared to that of the corresponding ITCs.

The Isle of Wight is pioneering the development of the UK's first truly sustainable region. The ambitious project promises islanders a 'utopia' of lower living costs, better quality of life, and a lighter carbon footprint.

Synthesis and anti-melanoma activity of various naphthalimide analogs, rationally modified by introducing isothiocyanate (ITC) and thiourea (TU) functionalities, found in well-known anti-cancer agents, is described. The structure–activity relationship comparison of the novel agents in inhibiting cancer cell growth was evaluated in various melanoma cell lines. Both ITC and TU analogs effectively inhibited cell viability and induced apoptosis in various human melanoma cells. Nitro substitution and increase in alkyl chain length, in general, enhanced the apoptotic activity of ITC derivatives. All the new compounds were well tolerated when injected intraperitoneal (i.p.) in mice at effective doses at which both the ITC and TU derivatives inhibited melanoma tumor growth in mice following i.p. xenograft. The nitro substituted naphthalimide–ITC derivative 3d was found to be the most effective in inducing apoptosis, and in inhibiting melanoma cell and tumor growth.

The article deals with the wide range of fuel cell technologies in a variety of applications. The company behind it believes that it is a major step forward in the development of solid oxide fuel cell technology for stationary power applications. Not only will the fuel cell power plant provide heat and electricity to several homes at the site on the outskirts of Vaasa, Finland, it will highlight the challenges that need to be overcome to get commercial fuel cell units to the mass market.

This paper discusses the revival of compressed air energy storage (CAES), though not a well-known technology, yet it has been around for years.

In the heart of the Middle East's oil-rich nations, the tiny Emirate of Abu Dhabi is pinning its economic future on innovative, renewable and low-carbon energy technologies. The author looks at Masdar city, a purpose-built 'ecopolis' designed to showcase the fruits of its investment that is at the heart of this multi-billion dollar initiative.

Introduction We have recently mapped ALS spatial risk in Ireland using Bayesian and cluster analysis methods at electoral division (ED) and small area (SA) levels. As a number of metal elements (both minerals and toxins) have been proposed as risk factors for ALS, here we extend this analysis to include soil constituents from the Irish National Soils Database as Bayesian conditional auto-regression covariates to determine associations with small area ALS risk. Methods Data on 45 different soil parameters were obtained under license from National Soils Database (via Irish EPA). We interpolated average values of each soil constituent for each small area using ordinary kriging. All cases of ALS in Ireland from January 1995 to December 2013 were identified from the Irish ALS register and observed and age and gender standardised expected cases were calculated for each SA. Besag-York-Mollie (BYM) models were then built including each parameter from the national soils database in turn as a Bayesian covariate in the BYM model. Models were compared using the deviance information criterion (DIC) and separate models were built for ALS subtypes. Results 1701 ALS patients were included – 959 (56%) were male, 938 (55%) had limb onset ALS. 315 Bayesian models were built in total. Of the 315 models built, only one resulted in a coefficient that did not overlap zero. For limb onset cases, total magnesium had a mean coefficient of 0.319 (credible interval 0.033–0.607). Discussion We report the first spatial analysis of potential association between ALS and soil minerals using a population-based dataset collected over 18 years. Our sole non-zero finding is likely a random finding due to the high number of models built. We did not find any evidence to support soil mineral and toxin levels as risk factors for ALS. However as soil parameters are an ecological assessment of exposure in a given area, individual level measures of exposure are required.

Objective: Few spatial cluster analyses of amyotrophic lateral sclerosis (ALS) incidence have been conducted on prospective incident population-based cohorts; we report results of a formal cluster analysis of the Irish ALS cohort from January 1, 1995, to December 31, 2013. Methods: We identified 1,684 incident cases from the Irish ALS register. Population data from 4 census years were used to calculate age- and sex-standardized expected ALS cases for 3,355 areas. Spatial cluster analysis was performed to identify high-risk clusters using both SaTScan and FleXScan software. Poisson-based, time period–stratified statistics and time-stratified Bayesian smoothed risk mapping were used to audit completeness of case ascertainment of the register. Results: No significant high-risk clusters of incident ALS were identified. However, SaTScan revealed 2 significant areas of lower-than-average ALS risk—one centered on County Kilkenny (relative risk 0.53, p = 0.012) and a smaller area in County Clare (relative risk 0.0, p = 0.029). Audit of case ascertainment did not indicate any failure to detect cases in these areas. Conclusions: The absence of high-risk ALS clusters in Ireland contrasts with previous studies. Our study has several advantages, notably the use of a long-running prospective ALS register with nationwide case ascertainment. The presence of 2 low-risk areas was unexpected. No obvious ascertainment, demographic, or common environmental factors explain this finding. However, we postulate that historical factors may have led to altered genetic admixture in these regions, possibly contributing to lower rates.

Synthesis and anti-melanoma activity of various naphthalimide analogs, rationally modified by introducing isothiocyanate (ITC) and thiourea (TU) functionalities, found in well-known anti-cancer agents, is described. The structure–activity relationship comparison of the novel agents in inhibiting cancer cell growth was evaluated in various melanoma cell lines. Both ITC and TU analogs effectively inhibited cell viability and induced apoptosis in various human melanoma cells. Nitro substitution and increase in alkyl chain length, in general, enhanced the apoptotic activity of ITC derivatives. All the new compounds were well tolerated when injected intraperitoneal (i.p.) in mice at effective doses at which both the ITC and TU derivatives inhibited melanoma tumor growth in mice following i.p. xenograft. The nitro substituted naphthalimide–ITC derivative 3d was found to be the most effective in inducing apoptosis, and in inhibiting melanoma cell and tumor growth.

Lung cancer remains one of the most preventable forms of cancer with about 90% of cases attributed to cigarette smoking. Over the years, the development of chemopreventive agents that could inhibit, delay, or reverse the lung carcinogenesis process has been an active field of research, however, without much attainment. Through extensive structure–activity relationship studies, we recently identified a novel agent phenylbutyl isoselenocyanate (ISC-4), designed on the basis of naturally occurring isothiocyanates well known for their lung cancer prevention properties, as a potential chemopreventive agent. In this study, we used A/J mice to evaluate the lung cancer chemopreventive potential of ISC-4. A single intragastric dose of 1.25 μmol ISC-4 resulted in a time-dependent increase of selenium levels in serum, liver, and lung, suggesting that ISC-4 is orally bioavailable, a key requirement for a chemopreventive agent. This dose also resulted in a time-dependent inhibition of microsomal cytochrome P450 (Cyp450) activity and delayed increases in phase II UDP-glucuronyl transferase (Ugt) and glutathione-S-transferase (Gst) activity. ISC-4 was able to induce mRNA expression of Cyp, Ugt, and Gst enzyme isoforms in liver, but in lung, it inhibited Cyp isoforms while inducing Ugt and Gst isoforms. In addition, ISC-4 effectively inhibited methyl–DNA adduct formation in mice fed diet supplemented with ISC-4 for two weeks and then treated with the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. These results suggest that ISC-4 is a strong candidate for development as a chemopreventive agent. Cancer Prev Res; 4(11); 1884–94. ©2011 AACR.

Introduction There has been much interest in spatial analysis of ALS to identify potential environmental or genetically caused clusters of disease. Results to date have been inconclusive. The Irish ALS register has been recently geocoded, presenting opportunity to perform a spatial analysis on national prospectively gathered data of incident cases over an 18-year period. Methods 1,645 cases of ALS in Ireland from January 1995 to July 2013 were identified from the Irish ALS register. 1,638 cases were successfully geocoded. Census data from four censuses: 1996, 2002, 2006 & 2011 were used to calculate an average population for the period and standardized incidence rates (SIRs) were calculated for 3,355 areas (Electoral Divisions). Bayesian conditional auto-regression was applied to produce smoothed relative risks (RR). These were then mapped for all cases, males & females separately, and those under 55 vs over 55 at diagnosis. Bayesian and linear regression were used to examine the relationship between population density and RR. Results Smoothed maps revealed no overall geographical pattern to ALS incidence in Ireland, although several areas of localized increased risk were identified. Stratified maps also suggested localized areas of increased RR, while dual analysis of the relationship between population density and RR of ALS yielded conflicting results, linear regression revealed a weak relationship. Discussion In contrast to some previous studies our analysis did not reveal any large-scale geographic patterns of incidence, yet localized areas of moderately high risk were found in both urban and rural areas. Stratified maps by age revealed a larger number of cases in younger people in the area of County Cork - possibly of genetic cause. Bayesian auto-regression of population density failed to find a significant association with risk, however weighted linear regression of post Bayesian smoothed Risk revealed an association between population density and increased ALS risk.

This chapter looks at the intertwined evolution of two different ideas throughout the past century: that of ‘territory’, that has been reshaped and redefined in the field of architecture and urbanism, and that of ‘digital’, that while becoming dominant, has been influencing territorial studies. While territory emerged as a subject, as the largescale object where to observe urbanization and landscape, the question of its representation becomes key in understanding its interaction with another emerging field, that of ‘digital’. It is thus through the representation of territory that this chapter conjugates digital and territorial turn. More in particular, we observe cartographies as and made by architects and urbanist, that we define transformative: with this notion, we intend cartography oriented not only to represent, but also to transform of the same object of representation, that is to say the territory itself. The digital evolution of transformative cartographies builds up from two parallel paths, that of an emerging physical territorial dimension and that of emerging technologies. Paths that converge and diverge over the decades: after a crossing turn between 8’0s and 90s, a forking path seems to rather distinguish the most recent experiences.