The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

INTRODUCTION: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up. RESULTS: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093). CONCLUSION: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned

Increasing awareness and reputation of MERCK S.A. Portugal through employee advocacy

Merck KGaA is a global Science and Technology company, focusing on the Healthcare Industry, Life Science and Performance Materials. Merck in Portugal is a relatively small subsidiary with a midsized office employing approximately 114 employees. Merck S.A. Portugal focuses mainly on the Healthcare Market. As the company went through a major transformation in 2016, it created a need to communicate on a low cost basis and in an efficient way, using digital as its main channel. The current paper shows the implementation of an employee advocacy strategic plan as a solution to digital communication. Employee Advocacy is a new communications concept derived from employee social media usage and employee word of mouth. It has been noted that employee networks are wider than company’s own and employee word of mouth is more trustworthy. Before the tool could be implemented a research on what motivates employees to commit to Brand Citizenship Behavior was performed. Findings revealed that in the case of Merck S.A. Portugal employees individual internal drive and brand knowledge are factors affecting willingness to share on social media. Based on the results a series of internal strategies were applied on- and offline.info:eu-repo/semantics/acceptedVersio

Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential

To promote cell survival, the antiapoptotic factor Bcl-xL both inhibits Bax-induced mitochondrial outer membrane permeabilization and stabilizes mitochondrial inner membrane ion flux and thus overall mitochondrial energetic capacity

Soil penetration resistance analysis by multivariate and geostatistical methods

The penetration resistance (PR) is a soil attribute that allows identifies areas with restrictions due to compaction, which results in mechanical impedance for root growth and reduced crop yield. The aim of this study was to characterize the PR of an agricultural soil by geostatistical and multivariate analysis. Sampling was done randomly in 90 points up to 0.60 m depth. It was determined spatial distribution models of PR, and defined areas with mechanical impedance for roots growth. The PR showed a random distribution to 0.55 and 0.60 m depth. PR in other depths analyzed showed spatial dependence, with adjustments to exponential and spherical models. The cluster analysis that considered sampling points allowed establishing areas with compaction problem identified in the maps by kriging interpolation. The analysis with main components identified three soil layers, where the middle layer showed the highest values of PR.La resistencia a la penetración (RP) es un atributo del suelo que permite identificar zonas con restricciones debido a la compactación, que se traduce en impedancia mecánica para el desarrollo de las raíces y en una menor productividad de los cultivos. El objetivo del presente trabajo fue caracterizar la RP de un suelo agrícola, mediante análisis geoestadístico y multivariado. El muestreo se realizó de manera aleatoria en 90 puntos, hasta una profundidad de 0,60 m. Se determinaron los modelos de distribución espacial de la RP y se delimitaron áreas con problemas de impedancia mecánica de las raíces. La RP presentó distribución aleatoria a 0,55 y 0,60 m de profundidad. La RP en las otras profundidades analizadas mostraron dependencia espacial, con ajustes a modelos exponenciales y esféricos. El análisis jerárquico que consideró puntos de muestreo, permitió establecer zonas con problemas de compactación, identificadas en los mapas obtenidos mediante interpolación por kriging. El análisis de componentes principales permitió identificar tres capas de suelo, donde la capa intermedia fue la que presentó los mayores valores de RP

Come for the looks, stay for the personality? A mixed methods investigation of reacquisition and owner recommendation of Bulldogs, French Bulldogs and Pugs

Brachycephalic breeds are proliferating internationally, with dramatic rises in popularity juxtaposed with common and severe breed-related health problems. Physical appearance is as a dominant factor attracting owners to brachycephalic breeds; however, whether these owners will choose their current breed for future ownership and develop 'breed-loyalty' in the face of health problems is not yet known. The aims of this study were (1) to quantify levels of, and explore factors associated with, brachycephalic dog owners' intentions to: (i) reacquire and/or (ii) recommend their current breed to potential first-time dog owners, and (2) to use qualitative methods to explore why brachycephalic dog owners would or would not recommend their current breed. This large mixed methods study reports on 2168 owners of brachycephalic breeds (Pugs: n = 789; French Bulldog: n = 741; Bulldogs: n = 638). Owners were highly likely to want to own their breed again in the future (93.0%) and recommend their breed to other owners (65.5%). Statistical modelling identified that first-time ownership and increased strength of the dog-owner relationship increased the likelihood of reacquisi-tion and/or recommendation. In contrast, an increased number of health problems, positive perception of their dog's health compared with the rest of their breed, and dog behaviour being worse than expected decreased the likelihood of reacquisition and/or recommendation. Thematic analyses constructed three themes describing why owners recommend their breed: positive behavioural attributes for a companion dog, breed suited to a sedentary lifestyle with limited space, and suitability for households with children. Five themes described why owners recommended against their breed: high prevalence of health problems, expense of ownership, ethical and welfare issues associated with breeding brachycephalic dogs, negative effects upon owner lifestyle and negative behavioural attributes. Understanding how breed-loyalty develops, and whether it can be attenuated, will be key to controlling the current population boom in brachycephalic breeds in the long-term

2-Deoxy-D-Glucose Treatment Induces Ketogenesis, Sustains Mitochondrial Function, and Reduces Pathology in Female Mouse Model of Alzheimer's Disease

Previously, we demonstrated that mitochondrial bioenergetic deficits preceded Alzheimer's disease (AD) pathology in the female triple-transgenic AD (3xTgAD) mouse model. In parallel, 3xTgAD mice exhibited elevated expression of ketogenic markers, indicating a compensatory mechanism for energy production in brain. This compensatory response to generate an alternative fuel source was temporary and diminished with disease progression. To determine whether this compensatory alternative fuel system could be sustained, we investigated the impact of 2-deoxy-D-glucose (2-DG), a compound known to induce ketogenesis, on bioenergetic function and AD pathology burden in brain. 6-month-old female 3xTgAD mice were fed either a regular diet (AIN-93G) or a diet containing 0.04% 2-DG for 7 weeks. 2-DG diet significantly increased serum ketone body level and brain expression of enzymes required for ketone body metabolism. The 2-DG-induced maintenance of mitochondrial bioenergetics was paralleled by simultaneous reduction in oxidative stress. Further, 2-DG treated mice exhibited a significant reduction of both amyloid precursor protein (APP) and amyloid beta (Aβ) oligomers, which was paralleled by significantly increased α-secretase and decreased γ-secretase expression, indicating that 2-DG induced a shift towards a non-amyloidogenic pathway. In addition, 2-DG increased expression of genes involved in Aβ clearance pathways, degradation, sequestering, and transport. Concomitant with increased bioenergetic capacity and reduced β-amyloid burden, 2-DG significantly increased expression of neurotrophic growth factors, BDNF and NGF. Results of these analyses demonstrate that dietary 2-DG treatment increased ketogenesis and ketone metabolism, enhanced mitochondrial bioenergetic capacity, reduced β-amyloid generation and increased mechanisms of β-amyloid clearance. Further, these data link bioenergetic capacity with β-amyloid generation and demonstrate that β-amyloid burden was dynamic and reversible, as 2-DG reduced activation of the amyloidogenic pathway and increased mechanisms of β-amyloid clearance. Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated β-amyloid burden