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Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades. Most recently, there has been considerable interest in the effect of CDKN2A and/or CDKN2B (CDKN2A/B) homozygous deletions (HD) on the prognosis of isocitrate dehydrogenase (IDH)-mutant astrocytomas. This is highlighted by the adoption of CDKN2A/B HD as an essential criterion for astrocytoma and IDH-mutant central nervous system (CNS) WHO grade 4 in the fifth edition of the World Health Organisation (WHO) Classification of Central Nervous System Tumours (2021). The CDKN2A and CDKN2B genes are located on the short arm of chromosome 9. CDKN2A encodes for two proteins, p14 and p16, and CDKN2B encodes for p15. These proteins regulate cell growth and angiogenesis. Interpreting the impact of CDKN2A/B alterations on astrocytoma prognosis is complicated by recent changes in tumour classification and a lack of uniform standards for testing CDKN2A/B. While the prognostic impact of CDKN2A/B HD is established, the role of different CDKN2A/B alterations—heterozygous deletions (HeD), point mutations, and promoter methylation—is less clear. Consequently, how these alternations should be incorporated into patient management remains controversial. To this end, we reviewed the literature on different CDKN2A/B alterations in IDH-mutant astrocytomas and their impact on diagnosis and management. We also provided a historical review of the changing impact of CDKN2A/B alterations as glioma classification has evolved over time. Through this historical context, we demonstrate that CDKN2A/B HD is an important negative prognostic marker in IDH-mutant astrocytomas; however, the historical data is challenging to interpret given changes in tumour classification over time, variation in the quality of evidence, and variations in the techniques used to identify CDKN2A/B deletions. Therefore, future prospective studies using uniform classification and detection techniques are required to improve the clinical interpretation of this molecular marker.

Both IDH1 (isocitrate dehydrogenase 1) and IDH2 (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both IDH1 and IDH2 mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis. Interrogation of cancer genomic databases and a systematic review was undertaken, demonstrating the rarity of the co-occurrence of IDH1 and IDH2 mutations in a variety of cancer types, and in glioma specifically. Due to the favourable outcome observed in this patient, the potential effect of concurrent IDH1 and IDH2 mutations on survival was also investigated.

Background: 177 LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer with trials adopting a standardised dose interval. Adjusting treatment intervals utilising early response biomarkers may improve patient outcomes. Objective: This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising 177 LuPSMA 24-h SPECT/CT ( 177 Lu-SPECT) and early prostate-specific antigen (PSA) response. Design: Retrospective analysis of a clinical 177 Lu-PSMA-I&T treatment programme. Methods: In all, 125 men were treated with 6-weekly 177 LuPSMA-I&T [median 3 cycles, interquartile range (IQR): 2–4], median dose 8.0 GBq [95% confidence interval (CI): 7.5–8.0]. Imaging screening involved 68 GaPSMA-11 PET/diagnostic CT. 177 Lu-SPECT/diagnostic CT was acquired following each therapy, and clinical assessments 3-weekly. Following dose 2 (week 6), a composite PSA and 177 Lu-SPECT/CT imaging response [partial response (PR), stable disease (SD), and progressive disease (PD)] determined ongoing management. Response group (RG) 1 (marked reduction in PSA/imaging PR) break in treatment until subsequent PSA rise, then re-treatment. RG 2 (stable or reduced PSA and/or imaging SD) 6-weekly treatments until six doses, or no longer clinically benefitting. RG 3 (rise in PSA and/or imaging PD) recommended for an alternative treatment. Results: Overall PSA50% response rate (PSARR) was 60% (75/125), median PSA-PFS 6.1 months (95%CI: 5.5–6.7), and median OS 16.8 months (95%CI: 13.5–20.1). 35% (41/116) were classified as RG 1, 34% (39/116) RG 2, and 31% (36/116) RG 3. PSARRs by RG were 95% (38/41), 74% (29/39), and 8% (3/36); median PSA-PFS rates were 12.1 months (95%CI: 9.3–17.4), 6.1 months (95%CI: 5.8–9.0), and 2.6 months (95%CI: 1.6–3.1); and OS rates were 19.2 months (95%CI: 16.8–20.7), 13.2 months (95%CI: 12.0–18.8), and 11.2 months (95%CI: 8.7–15.6) for RG 1, 2, and 3, respectively. The median months of ‘treatment holiday’ for RG 1 was 6.1 months (IQR: 3.4–8.7). Nine men had received prior 177 LuPSMA-617 and were retreated with 177 LuPSMA-I&T, with a PSARR of 56% on re-treatment. Conclusion: Personalising dosing regimens using early response biomarkers with 177 LuPSMA has the potential to achieve similar treatment responses to continuous dosing while allowing treatment breaks or intensification. Further evaluation of early response biomarker-guided treatment regimens in prospective trials is warranted. Plain Language Summary Lutetium-PSMA therapy is a new therapy for metastatic prostate cancer that is well tolerated and effective. However, not all men respond equally, with some responding very well and others progressing early. Personalising treatments require tools that can accurately measure treatment responses, preferably early in the treatment course, so adjustments to treatment can be made. Lutetium-PSMA can measure tumour sites after each therapy by taking whole body 3D images at 24 h using a small radiation wave from the treatment itself. This is called a SPECT scan. Previous work has shown that both prostate-specific antigen (PSA) response and changes in tumour volume on a SPECT scan can predict how patients will respond to treatment as early as dose 2. This study demonstrates that stratifying how men are treated based on the results of the 6-week SPECT scan and PSA response potentially allows a third of men to have break in treatment and that these men have both longer time to disease progression and OS. Men with an increase in tumour volume and increase in PSA early in treatment (6 weeks) had shorter time to disease progression and OS. Men with early biomarker disease progression were offered alternative treatments early in an attempt to allow the opportunity to allow a more effective potential therapy, if one was available. The study is an analysis of a clinical programme, and was not a prospective trial. As such, there are potential biases that could influence results. Hence, while the study is encouraging for the use of early response biomarkers to guide better treatment decisions, this must be validated in a well-designed clinical trial.

We are rapidly approaching a future in which cancer patient digital twins will reach their potential to predict cancer prevention, diagnosis, and treatment in individual patients. This will be realized based on advances in high performance computing, computational modeling, and an expanding repertoire of observational data across multiple scales and modalities. In 2020, the US National Cancer Institute, and the US Department of Energy, through a trans-disciplinary research community at the intersection of advanced computing and cancer research, initiated team science collaborative projects to explore the development and implementation of predictive Cancer Patient Digital Twins. Several diverse pilot projects were launched to provide key insights into important features of this emerging landscape and to determine the requirements for the development and adoption of cancer patient digital twins. Projects included exploring approaches to using a large cohort of digital twins to perform deep phenotyping and plan treatments at the individual level, prototyping self-learning digital twin platforms, using adaptive digital twin approaches to monitor treatment response and resistance, developing methods to integrate and fuse data and observations across multiple scales, and personalizing treatment based on cancer type. Collectively these efforts have yielded increased insights into the opportunities and challenges facing cancer patient digital twin approaches and helped define a path forward. Given the rapidly growing interest in patient digital twins, this manuscript provides a valuable early progress report of several CPDT pilot projects commenced in common, their overall aims, early progress, lessons learned and future directions that will increasingly involve the broader research community.

Background: Glioblastomas are the most common and fatal primary brain malignancy in adults. There is a growing interest in identifying the molecular mechanisms of these tumors to develop novel treatments. Glioblastoma neo-angiogenesis is driven by VEGF, and another potential molecule linked to angiogenesis is PSMA. Our study suggests the potential for an association between PSMA and VEGF expression in glioblastoma neo-vasculature. Methods: Archived IDH1/2 wild-type glioblastomas were accessed; demographic and clinical outcomes were recorded. PSMA and VEGF expression by IHC were examined. Patients were dichotomized into PSMA expression high (3+) and low (0–2+) groups. The association between PSMA and VEGF expression was evaluated using Chi2 analysis. OS in PSMA high and low expression groups were compared using multi-linear regression. Results: In total, 247 patients with IDH1/2 wild-type glioblastoma with archival tumor samples (between 2009–2014) were examined. PSMA expression correlated positively with VEGF expression (p = 0.01). We detected a significant difference in median OS between PSMA vascular endothelial expression high and low groups—16.1 and 10.8 months, respectively (p = 0.02). Conclusion: We found a potential positive correlation between PSMA and VEGF expression. Secondly, we showed a potential positive correlation between PSMA expression and overall survival.

Background: A CLCC1 c. 75C > A (p.D25E) mutation has been associated with autosomal recessive pigmentosa in patients in and from Pakistan. CLCC1 is ubiquitously expressed, and knockout models of this gene in zebrafish and mice are lethal in the embryonic period, suggesting that possible retinitis pigmentosa mutations in this gene might be limited to those leaving partial activity. In agreement with this hypothesis, the mutation is the only CLCC1 mutation associated with retinitis pigmentosa to date, and all identified patients with this mutation share a common SNP haplotype surrounding the mutation, suggesting a common founder.Methods: SNPs were genotyped by a combination of WGS and Sanger sequencing. The original founder haplotype, and recombination pathways were delineated by examination to minimize recombination events. Mutation age was estimated by four methods including an explicit solution, an iterative approach, a Bayesian approach and an approach based solely on ancestral segment lengths using high density SNP data.Results: All members of each of the nine families studied shared a single autozygous SNP haplotype for the CLCC1 region ranging from approximately 1–3.5 Mb in size. The haplotypes shared by the families could be derived from a single putative ancestral haplotype with at most two recombination events. Based on the haplotype and Gamma analysis, the estimated age of the founding mutation varied from 79 to 196 generations, or approximately 2,000–5,000 years, depending on the markers used in the estimate. The DMLE (Bayesian) estimates ranged from 2,160 generations assuming a population growth rate of 0–309 generations assuming a population growth rate of 2% with broad 95% confidence intervals.Conclusion: These results provide insight into the origin of the CLCC1 mutation in the Pakistan population. This mutation is estimated to have occurred 2000–5,000 years ago and has been transmitted to affected families of Pakistani origin in geographically dispersed locations around the world. This is the only mutation in CLCC1 identified to date, suggesting that the CLCC1 gene is under a high degree of constraint, probably imposed by functional requirements for this gene during embryonic development.

Raspberry (Rosales: Rosaceae) production in the U.K. has moved rapidly in the last 10 years to under polythene, combined with a reduced availability of broad-spectrum fungicides. Hence, the incidence of previously less prevalent diseases, such as Cladosporium (Capnodiales: Cladosporiaceae), has largely increased. This study aimed to identify the predominant Cladosporium species on raspberry and to understand the nature of its infection on raspberry fruit. Raspberries were collected from farms across the U.K. and Spain and incubated; fungal isolates were then isolated from typical Cladosporium lesions and identified to the species level based on the sequences of the trans elongation factor α and actin genes. Cladosporium cladosporioides (Fres) de Vries was confirmed as the predominant species responsible for infecting raspberry fruit close to harvest on fruit from the U.K. and Spain, being present on 41.5% of U.K. fruit and 84.6% of Spanish fruit. Raspberries were subsequently inoculated at different developmental stages with C. cladosporioides isolates to determine the susceptibility to Cladosporium skin lesions and stigmata infections in relation to the developmental stage. Only the ripening and ripe raspberries were susceptible to Cladosporium, resulting in skin lesions. Cladosporium can colonise the stigmata of raspberries earlier in fruit development and future research is required to determine if such stigmata infections could cause subsequent skin lesion infections. This study has provided the necessary epidemiological information to develop effective management measures against the Cladosporium species.

Abstract Background To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7th versus the 8th Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems. Methods All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007–2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/− neoadjuvant chemotherapy for those with bulky disease were used. All patients were Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) staged at baseline and at intervals for up to 2 years post-treatment. Patients received parotid-sparing intensity modulated or volumetric modulated arc therapy with simultaneous integrated boost to either 70Gy in 35 fractions or 66Gy in 30 fractions. The overall survival (OS) was determined for each stage using the 7th Ed and subsequently with the updated 8th Ed staging system. Results One hundred fifty-three patients were analysed. Patient stage groupings varied between the 7th and 8th Eds respectively; Stage I (0.7% vs 64.7%), Stage II (8.5% vs 22.2%), stage III (21.6% vs 12.4%) and stage IV (69.3% vs 0.7%). In the 7th Ed, the 5 year probability of OS for stages I to III was 90%, versus stage IV 85.5%. There was no statistically significant difference between the staging groups (p = 0.85). In the 8th Ed there was a statistically significant difference in 5 year OS for stage I and stage II disease (96.9% vs 77.1% respectively; p

This paper promotes debate into varying aspects of practice that was produced as part of 'You Don’t Need Eyes To See, You Need Vision', a recent event which presented new work by artists Lee Campbell, Adrian Lee and Carali McCall. Using performance practice-as-research, the artists interrogated the following question: How can acts exploring visual negation be used to generate public pedagogy and what may it bring to the experience of removal of sight?

We compared seedling emergence and soil seed bank composition under an Acacia mangium plantation and an adjacent tropical heath forest in the Andulau Forest Reserve, Brunei Darussalam. Soil samples were collected from ten 20 x 20 m plots set up in three contrasting habitats: the Acacia plantation, the adjacent heath forest, and the transition zone in-between. Soil samples were subjected to smoke and heat treatments, following which seedling emergence was observed daily over a 12-week period. In a parallel investigation, variations in species richness, seed density and seed viability of the soil seed banks of the ten plots were investigated. Seedling emergence was significantly highest in the plantation and lowest in the heath forest plots respectively. However, no significant differences among treatments, and no significant treatment-habitat interactions were detected. Species richness, seed density and seed viability in the plantation plots were significantly lower than the transition zone and intact heath forest plots. A. mangium seeds were not recorded in the heath forest soil seed banks but were detected in the plantation and transition zone plots. Lower native plant species richness, seed density and viability in the A. mangium plantation could imply higher regeneration potential for the heath forest habitat if severe habitat destruction was to occur in this forest reserve. We suggest that proper plantation management practices and close monitoring of soil seed banks are the best mechanisms that could be adopted to minimize the gradual spread of invasive Acacias into natural tropical heath forests of Borneo.

Primary tumours originating from the pericardium are extremely rare. Previous studies have reported that these tumours account for only 6.7–12.8% of all mediastinal tumours with an overall prevalence of 0.001% to 0.007%. The majority of these tumours are benign lipomas or pericardial cysts. The most common pericardial malignancy is mesothelioma. Sarcomas are soft-tissue mesenchymal malignancies originating from various parts of the body but are extremely rare in this area. We report a case of a 52-year-old female who was diagnosed with a primary sarcoma with rhabdoid differentiation originating from the pericardium. The patient presented to her GP with a four-week history of progressive dyspnea and chest pain on exertion. Chest X-Ray demonstrated a prominent pericardial effusion and suspicious chest and pericardial lesions. Biopsies of the effusion and primary tumour identified on FDG/PET scans revealed the diagnosis of primary undifferentiated sarcoma. On thoracotomy, it was noted that the tumour had invaded the right atrium; therefore, pericardial window was aborted and a drain inserted instead. The patient was then started on chemotherapy; however, progression soon occurred and the patient died within 4 months, suggesting there is urgent need for efficacious treatments for sarcomatous lesions.

In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET.Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling.Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13), or OS (RR 1.03; CI 0.77-1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04-1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82) and lower overall renal toxicity (RR 3.61; CI 1.24-10.51).Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET.

Raspberry (Rosales: Rosaceae) production in the U.K. has moved rapidly in the last 10 years to under polythene, combined with a reduced availability of broad-spectrum fungicides. Hence, the incidence of previously less prevalent diseases, such as Cladosporium (Capnodiales: Cladosporiaceae), has largely increased. This study aimed to identify the predominant Cladosporium species on raspberry and to understand the nature of its infection on raspberry fruit. Raspberries were collected from farms across the U.K. and Spain and incubated; fungal isolates were then isolated from typical Cladosporium lesions and identified to the species level based on the sequences of the trans elongation factor α and actin genes. Cladosporium cladosporioides (Fres) de Vries was confirmed as the predominant species responsible for infecting raspberry fruit close to harvest on fruit from the U.K. and Spain, being present on 41.5% of U.K. fruit and 84.6% of Spanish fruit. Raspberries were subsequently inoculated at different developmental stages with C. cladosporioides isolates to determine the susceptibility to Cladosporium skin lesions and stigmata infections in relation to the developmental stage. Only the ripening and ripe raspberries were susceptible to Cladosporium, resulting in skin lesions. Cladosporium can colonise the stigmata of raspberries earlier in fruit development and future research is required to determine if such stigmata infections could cause subsequent skin lesion infections. This study has provided the necessary epidemiological information to develop effective management measures against the Cladosporium species. [ABSTRACT FROM AUTHOR]

This article discusses the attitudes of police and police trainees toward corruption in Russia. The authors, analyzing data from a survey, conclude that the majority of?police and trainees view corruption in justifiable and?morally acceptable under certain conditions and for specific goals.

The present paper shows results of a proof-of-concept study on two historically related but geographically separated dialects of Swiss German. Between the 12th and 14th centuries, speakers of Valais German (southwestern Switzerland) emigrated to the southeastern part of the country, forming so-called Sprachinseln (enclaves) of Valais German in a Romansh-speaking area. Using an online survey, we collected responses from 300+ participants from the cantons of Valais and Grisons to examine how the two dialects have developed over time. Results suggest stability on the phonetic level, i. e. the two dialects still sound very similar despite having been geographically separated for 800 years. The morphosyntax and lexicon, however, exhibit substantial change. We discuss historic and sociodemographic factors that may explain these patterns.

Many language change studies aim for a partial revisitation, i.e., selecting survey sites from previous dialect studies. The central issue of survey site reduction, however, has often been addressed only qualitatively. Cluster analysis offers an innovative means of identifying the most representative survey sites among a set of original survey sites. In this paper, we present a general methodology for finding representative sites for an intended study, potentially applicable to any collection of data about dialects or linguistic variation. We elaborate the quantitative steps of the proposed methodology in the context of the “Linguistic Atlas of Japan” (LAJ). Next, we demonstrate the full application of the methodology on the “Linguistic Atlas of German-speaking Switzerland” (Germ.: “Sprachatlas der Deutschen Schweiz”—SDS), with the explicit aim of selecting survey sites corresponding to the aims of the current project “Swiss German Dialects Across Time and Space” (SDATS), which revisits SDS 70 years later. We find that depending on the circumstances and requirements of a study, the proposed methodology, introducing cluster analysis into the survey site reduction process, allows for a greater objectivity in comparison to traditional approaches. We suggest, however, that the suitability of any set of candidate survey sites resulting from the proposed methodology be rigorously revised by experts due to potential incongruences, such as the overlap of objectives and variables across the original and intended studies and ongoing dialect change.

This study examines the status of nonmodal phonation (e.g. breathy and creaky voice) in British English using smartphone recordings from over 2,500 speakers. With this novel data collection method, it uncovers effects that have not been reported in past work, such as a relationship between speakers’ education and their production of nonmodal phonation. The results also confirm that previous findings on nonmodal phonation, including the greater use of creaky voice by male speakers than female speakers, extend to a much larger and more diverse sample than has been considered previously. This confirmation supports the validity of using crowd-sourced data for phonetic analyses. The acoustic correlates that were examined include fundamental frequency, H1*-H2*, cepstral peak prominence, and harmonic-to-noise ratio.

In this paper, we present a novel computational approach to the analysis of accent variation. The case study is dialect leveling in the North of England, manifested as reduction of accent variation across the North and emergence of General Northern English (GNE), a pan-regional standard accent associated with middle-class speakers. We investigated this instance of dialect leveling using random forest classification, with audio data from a crowd-sourced corpus of 105 urban, mostly highly-educated speakers from five northern UK cities: Leeds, Liverpool, Manchester, Newcastle upon Tyne, and Sheffield. We trained random forest models to identify individual northern cities from a sample of other northern accents, based on first two formant measurements of full vowel systems. We tested the models using unseen data. We relied on undersampling, bagging (bootstrap aggregation) and leave-one-out cross-validation to address some challenges associated with the data set, such as unbalanced data and relatively small sample size. The accuracy of classification provides us with a measure of relative similarity between different pairs of cities, while calculating conditional feature importance allows us to identify which input features (which vowels and which formants) have the largest influence in the prediction. We do find a considerable degree of leveling, especially between Manchester, Leeds and Sheffield, although some differences persist. The features that contribute to these differences most systematically are typically not the ones discussed in previous dialect descriptions. We propose that the most systematic regional features are also not salient, and as such, they serve as sociolinguistic regional indicators. We supplement the random forest results with a more traditional variationist description of by-city vowel systems, and we use both sources of evidence to inform a description of the vowels of General Northern English.

This study aimed to identify the effects of different kick types on the relationship between kicking leg muscle activation and ball velocity. The muscle activation of selected knee extensor and flexor muscles of 10 amateur soccer players were measured using electromyography during the performance of six maximal soccer kick types. The highest ball velocity was achieved by the instep kick (96.2 km/hr-1), followed by the lofted kick, the inside curve kick, the outside kick, the outside curve kick, and finally the inside kick (81.3 km/hr-1). There were significant positive correlations between muscle activation and ball velocity for the vastus lateralis and lofted (0.765), inside curve (0.792) and instep kicks (0.788), and for the gastrocnemious with the outside kick (0.796). Non-significant correlations between muscle activation and ball velocity exhibited a trend such that they were positive for the vastus medialis and vastus lateralis but negative for the biceps femoris and gastrocnemious for inside-foot-dominated kicks, while this trend was reversed for outside-foot-dominated kicks. According to results, the noted trends can be explained by the change in muscle activation patterns required to orientate the foot for each type of kick; this has implications for players’ training activities.

In this paper, we present the English Dialects App (EDA) and the English Dialects App Corpus (EDAC). EDA is a free iOS and Android app, launched in January 2016 that features a dialect quiz and dialect recordings. For the quiz, users indicate which variants of 26 words they use and the application guesses their local dialect; for the recordings, users can record a short text. The result is EDAC which includes metadata on mobility, ethnicity, age, educational level, and gender. More than 47,000 users from across the UK have indicated dialect variants for these 26 words, and more than 3,500 users have provided audio recordings. Unavoidably, EDAC does not successfully reflect distributions of age, ethnicity, qualification levels, and other parameters found for the UK population given that smartphone-based research reaches a specific stratum of the population. Yet there are also clear benefits to the sampling strategy used – benefits and pitfalls are discussed in this article. Future analyses will provide the most comprehensive understanding of English regional dialect variation since the work of the traditional dialectologists. We showcase two such analyses in this article. EDAC should, we demonstrate, be of interest to researchers in dialectology but also in forensic phonetics.

Immunization with a whole-cell sonicate vaccine of Helicobacter fells in conjunction with cholera toxin as a mucosal adjuvant induces long-term protective immunity in a majority of laboratory mice. We have combined gene expression profiling and immunohistochemical analysis on a set of immunized animals to better understand the mechanism of protection. The stomachs of protected animals exhibited a strikingly different transcriptional profile compared with those of nonprotected or control mice, indicatlng that vaccination targets the appropriate site and leaves a molecular signature. Among the genes whose up-regulation is significantly correlated with protection are a number of adipocytespecific factors. These include the fat-cell-specific cytokines adipsin, resistin, and adiponectin and the adipocyte surface marker CD36. Interestingly, potentially protective T and B lymphocytes can be found embedded in the adipose tissue surrounding protected stomachs but never in control or unprotected stomachs. Adipsinspecific immunohistochemical staining of protected stomach sections further revealed molecular cross-talk between adjacent lymphoid and adipose cell populations. We propose a mechanism of protection that involves the effector responses of either or both lymphocyte subclasses as well as the previously unappreciated paracrine functions of adipose tissue surrounding the resident lymphocytes. [ABSTRACT FROM AUTHOR]

The present study deals with the areal variation of /r/-realisations in the Alemannic dialects spoken in Switzerland. In particular, we provide a quantitative survey of recordings collected through crowdsourcing, i. e. by means of the smartphone application Dialäkt Äpp (Leemann/Kolly 2013). Each of the 2851 recordings of the word trinke (‘to drink’) was auditorily coded by at least two of the four authors. The resulting maps show a neat areal distribution of the realisations of /r/, with alveolar variants in most of the central Midlands and in the Alpine regions. Uvular variants, on the other hand, seem to prevail in the northeastern and northwestern parts of German-speaking Switzerland. Comparing our data with traditional dialectological sources, we find evidence for the hypothesis that the alveolar realisation of /r/ has been extensively replaced by uvular variants in large parts of the northeast; apparently, a similar sound change is now in progress in the rural areas around Basel.

Research on regional linguistic variation typically involves data collection in the field. This process itself can take up several months if not years. In the present study we demonstrate how we can use web interactives in collaboration with media outlets for a fast gathering of regional, sociolinguistic data. In collaboration with SPIEGEL ONLINE and Tagesanzeiger, we developed a web interactive that predicts users' regional backgrounds from within German-speaking Europe. More than 1.9M people have participated in the interactive, more than 770K users have provided metadata. Said metadata allowed us to capture regional variation in language as of today, which we can compare to historical survey data-enabling us to track the evolution of German in Europe over the past 40 years. We report on regional levelling of lexical variants, a process which appears to be particularly prevalent in the northern parts of German-speaking Europe. We further found an effect of (former) national and regional borders on language use. This innovative paradigm allows us to collect sociolinguistic data of an unprecedented scale-at the same time it presents significant challenges, both of which-benefits and challenges-will be discussed in this contribution.

Crowdsourcing linguistic phenomena with smartphone applications is relatively new. In linguistics, apps have predominantly been developed to create pronunciation dictionaries, to train acoustic models, and to archive endangered languages. This paper presents the first account of how apps can be used to collect data suitable for documenting language change: we created an app, Dialäkt Äpp (DÄ), which predicts users' dialects. For 16 linguistic variables, users select a dialectal variant from a drop-down menu. DÄ then geographically locates the user's dialect by suggesting a list of communes where dialect variants most similar to their choices are used. Underlying this prediction are 16 maps from the historical Linguistic Atlas of German-speaking Switzerland, which documents the linguistic situation around 1950. Where users disagree with the prediction, they can indicate what they consider to be their dialect's location. With this information, the 16 variables can be assessed for language change. Thanks to the playfulness of its functionality, DÄ has reached many users; our linguistic analyses are based on data from nearly 60,000 speakers. Results reveal a relative stability for phonetic variables, while lexical and morphological variables seem more prone to change. Crowdsourcing large amounts of dialect data with smartphone apps has the potential to complement existing data collection techniques and to provide evidence that traditional methods cannot, with normal resources, hope to gather. Nonetheless, it is important to emphasize a range of methodological caveats, including sparse knowledge of users' linguistic backgrounds (users only indicate age, sex) and users' self-declaration of their dialect. These are discussed and evaluated in detail here. Findings remain intriguing nevertheless: as a means of quality control, we report that traditional dialectological methods have revealed trends similar to those found by the app. This underlines the validity of the crowdsourcing method. We are presently extending DÄ architecture to other languages.