43 research outputs found
Wenn Bartonellen ihre Anker auswerfen : Bartonella henselae verbindet Infektionsforschung mit BlutgefĂ€Ăwachstum
Bei gesunden Menschen verlĂ€uft die Infektion mit Bartonella henselae als vergleichsweise harmlose "Katzenkratzkrankheit". Erst mit Beginn der AIDS-Pandemie zeigte sich, dass das Bakterium bei immungeschwĂ€chten Patienten auch die pathologische Neubildung von BlutgefĂ€Ăen auslösen kann. Diese PathogenitĂ€tsstrategie unterscheidet die Spezies der Bartonellen von allen anderen bakteriellen Infektionserregern des Menschen. FĂŒr Mikrobiologen ist Bartonella henselae deshalb ein interessanter Modellorganismus, weil BlutgefĂ€Ăwachstum in erster Linie eine DomĂ€ne der Tumorforschung ist
#nosnowflakes: the toleration of harassment and an emergent gender-related digital divide, in a UK student online culture
In recent years, some political commentators and mainstream media outlets in the United Kingdom have pejoratively labelled young people, especially university students, a âsnowflake generationâ â a term used to mock their perceived intolerance and over-sensitivity (Fox, 2016; Gullis, 2017; Slater, 2016; Talbot, 2020). This article challenges this discourse by drawing on findings from a large-scale study (N = 810) conducted on a university campus in England that critically examined studentâs perceptions of and attitudes to different forms of online harassment, including abusive, offensive and harassing communications, using survey and interview data. Key findings indicate that online harassment is so pervasive in digitised spaces that it is often viewed as the ânormâ by the student population who appear willing to tolerate it, rather than take actions to address it, which challenges pejorative claims that they are intolerant and easily offended âsnowflakesâ. Respondents who identify as female and transgender are more likely to be targeted by online harassment. We argue that the label âsnowflake generationâ is diverting attention away from studentâs everyday experiences of online harassment and its adverse effects, particularly on women and transgendered people, which has the potential to create a gender-related digital divide (Jane, 2018). The implications of these findings for the higher education sector will be outlined
RETRACTED: Right to left ventricular volume ratio: A novel marker of disease severity in chronic thromboembolic pulmonary hypertension
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted after the journal was approached by its authors bringing important matters to our attention. It has been retracted for two reasons:1. because the statement that âall authors had seen and approved the manuscriptâ proved to be incorrect; and 2. because of uncertainties over informed consent being adequately documented. We were notified that an error occurred because of a misunderstanding between authors at different locations, concerning the nature of the Ethics approval that had been obtained from these patients.This new substudy, a retrospective analysis of their MRI data before and after surgery, was not separately submitted to relevant Ethics Committee nor was informed consent for the MRI substudy obtained from the patients
Flexible, Capable, Adaptable: A Dynamic Allied Health Workforce
Objective: The Allied Health Executive at a major Metropolitan Health Service was experiencing an increasing number of flexible work requests and was keen to ensure that local and legislative requirements were met, our highly skilled and specialist staff were supported to remain in the workforce as their life outside work changed and the operational demands of a bed-based service delivery model were not negatively impacted.
Design: A root cause analysis was completed identifying three main contributing factors for the current, adhoc approach to flexible work requests. Current and past flexible work participants were surveyed, along with their managers and the Nurse Unit Managers of the clinical work areas. A literature review and environmental scan regarding frameworks for decision making for and supporting flexible work requests was undertaken.
Findings: There was a lack of consistent information as to how to establish and manage a flexible work request. There had been an historical view that flexible work requests were difficult to operationalise and there were missed experiences with flexible work arrangements for the people involved, their managers and their colleagues.
Outcome measures: The combined data was then utilised to develop a framework to support decision-making around whether a role could operate as a flexible work arrangement. A framework on how to best support the staff considering and entering into these arrangements to ensure all the benefits of a flexible work arrangement are realised and many of the challenges minimised was also developed.
Conclusion: Flexible work arrangements should be considered in appropriate circumstances, and will have the best opportunity for success when supported by a consistent, evidenced-based framework.
Abbreviations: EFT â Equivalent Full Time; RCA â Root Cause Analysis
Prion diseases are efficiently transmitted by blood transfusion in sheep
The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected tranfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans. (Blood. 2008; 112: 4739-4745
Harmful Algal Bloom Bulletins
Use Case Title: Harmful Algal Blooms
Environmental matrix of interest (Air, Ice, Mar. Water, etc.): Marine
Study Regions: Shelf Seas in Norway, Ireland and Spain
Dissemination Method: Web
Providing near real-time and forecast information for the aquaculture industry along Europeâs Atlantic coast is of vital importance in mitigating the effects of HABs. In this task, In-situ and satellite data will be amalgamated in a decision support system. In-situ data include oceanographic data e.g. water column structure, current speeds, biological samples (e.g. algal toxins, phytoplankton cell counts, barcoding) and hydrographic and biogeochemical information where possible. The In-situ data will be used to inform and validate biophysical models and to produce circulation forecasts for the coming three to five days. These data will undergo expert interpretation to produce an early warning bulletin to the aquaculture industry in Spain, Norway and Ireland. The bulletin will be distributed over a specified production season to fish farmers and shellfish production facilities so that husbandry and harvesting techniques can reflect the prevailing HAB conditions at any point in time
TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms
[EN] Objective Hepatocellular carcinoma (HCC) is a prevalent
and aggressive cancer usually arising on a background
of chronic liver injury involving inflammatory and hepatic
regenerative processes. The triggering receptor expressed
on myeloid cells 2 (TREM-2) is predominantly expressed in
hepatic non-parenchymal
cells and inhibits Toll-like
receptor
signalling, protecting the liver from various hepatotoxic
injuries, yet its role in liver cancer is poorly defined. Here,
we investigated the impact of TREM-2 on liver regeneration
and hepatocarcinogenesis.
Design TREM-2 expression was analysed in liver tissues
of two independent cohorts of patients with HCC and
compared with control liver samples. Experimental HCC
and liver regeneration models in wild type and Trem-2-/-
mice, and in vitro studies with hepatic stellate cells (HSCs)
and HCC spheroids were conducted.
Results TREM-2 expression was upregulated in human
HCC tissue, in mouse models of liver regeneration and
HCC. Trem-2-/- mice developed more liver tumours
irrespective of size after diethylnitrosamine (DEN)
administration, displayed exacerbated liver damage,
inflammation, oxidative stress and hepatocyte proliferation.
Administering an antioxidant diet blocked DEN-induced
hepatocarcinogenesis in both genotypes. Similarly,
Trem-2-/- animals developed more and larger tumours in
fibrosis-associated
HCC models. Trem-2-/- livers showed
increased hepatocyte proliferation and inflammation after
partial hepatectomy. Conditioned media from human HSCs
overexpressing TREM-2 inhibited human HCC spheroid
growth in vitro through attenuated Wnt ligand secretion.
Conclusion TREM-2 plays a protective role in
hepatocarcinogenesis via different pleiotropic effects,
suggesting that TREM-2 agonism should be investigated
as it might beneficially impact HCC pathogenesis in a
multifactorial manner.Spanish Ministry of Economy and Competitiveness and âInstituto de Salud
Carlos IIIâ grants (MJP (PI14/00399, PI17/00022 and Ramon y Cajal Programme
RYC-2015â17755); JMB (PI12/00380, PI15/01132, PI18/01075, Miguel Servet
Programme CON14/00129 and CPII19/00008) cofinanced by âFondo Europeo de
Desarrollo Regionalâ (FEDER); CIBERehd: MJP, JMB and LB), Spain; IKERBASQUE,
Basque foundation for Science (MJP and JMB), Spain; âDiputaciĂłn Foral de Gipuzkoaâ
(MJP: DFG18/114, DFG19/081; JMB: DFG15/010, DFG16/004); BIOEF (Basque
Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/
BD to JMB); Department of Health of the Basque Country (MJP: 2015111100 and
2019111024; JMB: 2017111010), Euskadi RIS3 (JMB: 2016222001, 2017222014,
2018222029, 2019222054, 2020333010) Department of Industry of the Basque
Country (JMB: Elkartek: KK-2020/00008) and AECC Scientific Foundation (JMB).
AE-B
was funded by the University of the Basque Country (UPV/EHU) (PIF2014/11)
and by the short-term
training fellowship Andrew K Burroughs (European
Association for the Study of the Liver, EASL). IL and AA-L
were funded by the
Department of Education, Language Policy and Culture of the Basque Government
(PRE_2016_1_0152 and PRE_2018_1_0184). OS and SK were funded by the
Austrian Science Fund (FWF25801-B22,
FWF-P35168
to OS and L-Mac:
F 6104-B21
to SK). FO and DAM were funded by a UK Medical Research Council programme
Grant MR/R023026/1. DAM was also funded by the CRUK programme grant
C18342/A23390, CRUK/AECC/AIRC Accelerator Award A26813 and the MRC MICA
programme grant MR/R023026/1. JBA is supported by the Danish Medical Research
Council, Danish Cancer Society, Nordisk Foundation, and APM Foundation. CJOâR
and PM-G
are supported by Marie Sklodowska-Curie
Programme and EASL Sheila
Sherlock postdoctoral fellowships
Oral Abstracts 7: RA ClinicalO37.âLong-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach
Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naĂŻve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ÎmTSS â€0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMSâProvided Expert Advice, Undertaken Trials, AbbVieâAbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, NovartisâResearch Grants, Consultation Fees. S.F., AbbVieâEmployee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCBâResearch Grants, Consultation Fees. H.K., AbbVieâEmployee, Stocks. S.R., AbbVieâEmployee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCBâResearch Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB PharmaâConsultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ÎmTSS â€0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ÎmTSS â€0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ÎmTSS â€0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ÎmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain âŒ38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.
The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access