Thresholds for Abdominal Aortic Aneurysm Repair in England and the United States.

Background Thresholds for repair of abdominal aortic aneurysms vary considerably among countries. Methods We examined differences between England and the United States in the frequency of aneurysm repair, the mean aneurysm diameter at the time of the procedure, and rates of aneurysm rupture and aneurysm-related death. Data on the frequency of repair of intact (nonruptured) abdominal aortic aneurysms, in-hospital mortality among patients who had undergone aneurysm repair, and rates of aneurysm rupture during the period from 2005 through 2012 were extracted from the Hospital Episode Statistics database in England and the U.S. Nationwide Inpatient Sample. Data on the aneurysm diameter at the time of repair were extracted from the U.K. National Vascular Registry (2014 data) and from the U.S. National Surgical Quality Improvement Program (2013 data). Aneurysm-related mortality during the period from 2005 through 2012 was determined from data obtained from the Centers for Disease Control and Prevention and the U.K. Office of National Statistics. Data were adjusted with the use of direct standardization or conditional logistic regression for differences between England and the United States with respect to population age and sex. Results During the period from 2005 through 2012, a total of 29,300 patients in England and 278,921 patients in the United States underwent repair of intact abdominal aortic aneurysms. Aneurysm repair was less common in England than in the United States (odds ratio, 0.49; 95% confidence interval [CI], 0.48 to 0.49; P<0.001), and aneurysm-related death was more common in England than in the United States (odds ratio, 3.60; 95% CI, 3.55 to 3.64; P<0.001). Hospitalization due to an aneurysm rupture occurred more frequently in England than in the United States (odds ratio, 2.23; 95% CI, 2.19 to 2.27; P<0.001), and the mean aneurysm diameter at the time of repair was larger in England (63.7 mm vs. 58.3 mm, P<0.001). Conclusions We found a lower rate of repair of abdominal aortic aneurysms and a larger mean aneurysm diameter at the time of repair in England than in the United States and lower rates of aneurysm rupture and aneurysm-related death in the United States than in England. (Funded by the Circulation Foundation and others.)

Emotional cues enhance the attentional effects on spatial and temporal resolution

In the present study, we demonstrated that the emotional significance of a spatial cue enhances the effect of covert attention on spatial and temporal resolution (i.e., our ability to discriminate small spatial details and fast temporal flicker). Our results indicated that fearful face cues, as compared with neutral face cues, enhanced the attentional benefits in spatial resolution but also enhanced the attentional deficits in temporal resolution. Furthermore, we observed that the overall magnitudes of individuals’ attentional effects correlated strongly with the magnitude of the emotion × attention interaction effect. Combined, these findings provide strong support for the idea that emotion enhances the strength of a cue’s attentional response

Estrogens Can Disrupt Amphibian Mating Behavior

The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline

Survival processing in times of stress

Recent studies have found that processing information according to an evolutionary relevant (i.e., survival) scenario improves its subsequent memorability, potentially as a result of fitness advantages gained in the ancestral past. So far, research has not revealed much about any proximate mechanisms that might underlie this so-called survival processing advantage in memory. Intriguingly, research has shown that the memorability of stressful situations is enhanced via the release of stress hormones acting on brain regions involved in memory. Since survival situations habitually involve some degree of stress, in the present study, we investigated whether stress serves as a proximate mechanism to promote survival processing. Participants rated words for their relevance to either a survival or a neutral (moving) scenario after they had been exposed to a psychosocial stressor or a no-stress control condition. Surprise retention tests immediately following the rating task revealed that survival processing and acute stress independently boosted memory performance. These results therefore suggest that stress does not serve as a proximate mechanism of the survival processing advantage in memory

Forgetting having denied: The "amnesic" consequences of denial

The concept of denial has its roots in psychoanalysis. Denial has been assumed to be effective in blocking unwanted memories. In two experiments, we report that denial has unique consequences for remembering. In two experiments, participants viewed a video of a theft and half of the participants had to deny seeing certain details in the video whereas the other half had to tell the truth. One day later, all participants were given a source monitoring recognition or recall task. In these tasks, they were instructed to indicate (1) whether they could remember talking about certain details and (2) whether they could recollect seeing those details in the video. In both experiments, we found that denial made participants forget that they talked about these details while leaving memory for the video unaffected. This denial-induced forgetting was evident for both the source monitoring recognition and recall tests. Furthermore, when we asked participants after the experiment whether they could still not remember talking about these details, participants who had to deny were most likely to report that they forgot this. In contrast to a widely held belief, we show that denial does not impair memory for the experienced stimuli, but that it has a unique ability to undermine memory for what was talked about

Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts

<p>Abstract</p> <p>Background</p> <p>Baseline low platelet count (< 150,000/μL) increases the risk of on-treatment severe thrombocytopenia (platelet count < 50,000/μL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia.</p> <p>Methods</p> <p>Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy.</p> <p>Results</p> <p>Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count < 100,000/μL and rapid early platelet decline (> 30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (<it>P </it>< 0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT ≥ 100,000/μL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count < 100,000/μL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%).</p> <p>Conclusions</p> <p>For patients with CHC on antiviral therapy, baseline platelet counts < 100,000/μL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.</p

Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3 Transcriptional Activity by Increasing Its Nuclear Localization

Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN.TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation.Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis

Appraising the intention of other people: Ecological validity and procedures for investigating effects of lighting for pedestrians

One of the aims of outdoor lighting public spaces such as pathways and subsidiary roads is to help pedestrians to evaluate the intentions of other people. This paper discusses how a pedestrians’ appraisal of another persons’ intentions in artificially lit outdoor environments can be studied. We review the visual cues that might be used, and the experimental design with which effects of changes in lighting could be investigated to best resemble the pedestrian experience in artificially lit urban environments. Proposals are made to establish appropriate operationalisation of the identified visual cues, choice of methods and measurements representing critical situations. It is concluded that the intentions of other people should be evaluated using facial emotion recognition; eye tracking data suggest a tendency to make these observations at an interpersonal distance of 15 m and for a duration of 500 ms. Photographs are considered suitable for evaluating the effect of changes in light level and spectral power distribution. To support investigation of changes in spatial distribution further investigation is needed with 3D targets. Further data are also required to examine the influence of glare

Loss of Niemann-Pick C1 or C2 Protein Results in Similar Biochemical Changes Suggesting That These Proteins Function in a Common Lysosomal Pathway

Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely

Proteomics of industrial fungi: trends and insights for biotechnology

Filamentous fungi are widely known for their industrial applications, namely, the production of food-processing enzymes and metabolites such as antibiotics and organic acids. In the past decade, the full genome sequencing of filamentous fungi increased the potential to predict encoded proteins enormously, namely, hydrolytic enzymes or proteins involved in the biosynthesis of metabolites of interest. The integration of genome sequence information with possible phenotypes requires, however, the knowledge of all the proteins in the cell in a system-wise manner, given by proteomics. This review summarises the progress of proteomics and its importance for the study of biotechnological processes in filamentous fungi. A major step forward in proteomics was to couple protein separation with high-resolution mass spectrometry, allowing accurate protein quantification. Despite the fact that most fungal proteomic studies have been focused on proteins from mycelial extracts, many proteins are related to processes which are compartmentalised in the fungal cell, e.g. β-lactam antibiotic production in the microbody. For the study of such processes, a targeted approach is required, e.g. by organelle proteomics. Typical workflows for sample preparation in fungal organelle proteomics are discussed, including homogenisation and sub-cellular fractionation. Finally, examples are presented of fungal organelle proteomic studies, which have enlarged the knowledge on areas of interest to biotechnology, such as protein secretion, energy production or antibiotic biosynthesis