Tumors of the Foot and Ankle: A Single-institution Experience

Tumors of the foot and ankle are rare, and the particular clinicopathologic features, therapeutic approach, and outcomes in this setting are not well established. From January 2000 to December 2010, 72 patients with primary musculoskeletal tumors of the foot and ankle, both benign and malignant, were treated at a single institution. Of the 72 patients, 56% were female. The median age was 52 years. Of the 72 tumors, 62 (86.11%) were located in the foot and 10 were located in the ankle; 63 (87.5%) were soft tissue tumors and 9 (12.5%) were bone tumors. Overall, 56 (78%) were benign tumors and 16 (22%) were malignant tumors. The most frequent soft tissue and bone diagnosis was giant cell tumor. The median follow-up period was 49 months. The vast majority of the tumors were located in the foot. Benign tumors were dominant, outnumbering malignant tumors by more than 3 to 1. The diversity of the histologic benign types was evident, with giant cell tumor, angiomyoma, and lipoma the most frequent. Regarding the malignant tumors, a clear male predominance was present, the median age was 45 years, and the most frequent tumor was synoviosarcoma. The 9-year overall and disease-free survival rate was 65% and 40%, respectively

Free text adversity statements as part of a contextualised admissions process:a qualitative analysis

Abstract Background Medical schools globally are encouraged to widen access and participation for students from less privileged backgrounds. Many strategies have been implemented to address this inequality, but much still needs to be done to ensure fair access for all. In the literature, adverse circumstances include financial issues, poor educational experience and lack of professional-status parents. In order to take account of adverse circumstances faced by applicants, The University of Dundee School of Medicine offers applicants the opportunity to report circumstances which may have resulted in disadvantage. Applicants do this by completing a free text statement, known as an ‘adversity statement’, in addition to the other application information. This study analysed adversity statements submitted by applicants during two admissions cycles. Analysis of content and theme was done to identify the information applicants wished to be taken into consideration, and what range of adverse circumstances individuals reported. Methods This study used a qualitative approach with thematic analysis to categorise the adversity statements. The data was initially analysed to create a coding framework which was then applied to the whole data set. Each coded segment was then analysed for heterogeneity and homogeneity, segments merged into generated themes, or to create sub-themes. Results The data set comprised a total of 384 adversity statements. These showed a wide range of detail involving family, personal health, education and living circumstances. Some circumstances, such as geographical location, have been identified and explored in previous research, while others, such as long term health conditions, have had less attention in the literature. The degree of impact, the length of statement and degree of detail, demonstrated wide variation between submissions. Conclusions This study adds to the debate on best practice in contextual admissions and raises awareness of the range of circumstances and impact applicants wish to be considered. The themes which emerged from the data included family, school, personal health, and geographical location issues. Descriptions of the degree of impact that an adverse circumstance had on educational or other attainment was found to vary substantially from statements indicating minor, impact through to circumstances stated as causing major impact

Insight dimensions and cognitive function in psychosis: a longitudinal study

BACKGROUND: It has been reported that lack of insight is significantly associated with cognitive disturbance in schizophrenia. This study examines the longitudinal relationships between insight dimensions and cognitive performance in psychosis. METHODS: Participants were 75 consecutively admitted inpatients with schizophrenia, affective disorder with psychotic symptoms or schizoaffective disorder. Assessments were conducted at two time points during the study: at the time of hospital discharge after an acute psychotic episode and at a follow-up time that occurred more than 6 months after discharge. A multidimensional approach of insight was chosen and three instruments for its assessment were used: the Scale to Assess Unawareness of Mental Disorder (SUMD), three items concerning insight on the Assessment and Documentation in Psychopathology (AMDP) system and the Insight and Treatment Attitudes Questionnaire. The neuropsychological battery included a wide range of tests that assessed global cognitive function, attention, memory, and executive functions. RESULTS: After conducting adequate statistical correction to avoid Type I bias, insight dimensions and cognitive performance were not found to be significantly associated at cross-sectional and longitudinal assessments. In addition, baseline cognitive performance did not explain changes in insight dimensions at follow-up. Similar results were found in the subset of patients with schizophrenia (n = 37). The possibility of a Type II error might have increased due to sample attrition at follow-up. CONCLUSION: These results suggest that lack of insight dimensions and cognitive functioning may be unrelated phenomena in psychosis

Basal ganglia correlates of fatigue in young adults

Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward

Candida albicans Scavenges Host Zinc via Pra1 during Endothelial Invasion

The ability of pathogenic microorganisms to assimilate essential nutrients from their hosts is critical for pathogenesis. Here we report endothelial zinc sequestration by the major human fungal pathogen, Candida albicans. We hypothesised that, analogous to siderophore-mediated iron acquisition, C. albicans utilises an extracellular zinc scavenger for acquiring this essential metal. We postulated that such a “zincophore” system would consist of a secreted factor with zinc-binding properties, which can specifically reassociate with the fungal cell surface. In silico analysis of the C. albicans secretome for proteins with zinc binding motifs identified the pH-regulated antigen 1 (Pra1). Three-dimensional modelling of Pra1 indicated the presence of at least two zinc coordination sites. Indeed, recombinantly expressed Pra1 exhibited zinc binding properties in vitro. Deletion of PRA1 in C. albicans prevented fungal sequestration and utilisation of host zinc, and specifically blocked host cell damage in the absence of exogenous zinc. Phylogenetic analysis revealed that PRA1 arose in an ancient fungal lineage and developed synteny with ZRT1 (encoding a zinc transporter) before divergence of the Ascomycota and Basidiomycota. Structural modelling indicated physical interaction between Pra1 and Zrt1 and we confirmed this experimentally by demonstrating that Zrt1 was essential for binding of soluble Pra1 to the cell surface of C. albicans. Therefore, we have identified a novel metal acquisition system consisting of a secreted zinc scavenger (“zincophore”), which reassociates with the fungal cell. Furthermore, functional similarities with phylogenetically unrelated prokaryotic systems indicate that syntenic zinc acquisition loci have been independently selected during evolution

Synaptic Wnt signaling—a contributor to major psychiatric disorders?

Wnt signaling is a key pathway that helps organize development of the nervous system. It influences cell proliferation, cell fate, and cell migration in the developing nervous system, as well as axon guidance, dendrite development, and synapse formation. Given this wide range of roles, dysregulation of Wnt signaling could have any number of deleterious effects on neural development and thereby contribute in many different ways to the pathogenesis of neurodevelopmental disorders. Some major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders, are coming to be understood as subtle dysregulations of nervous system development, particularly of synapse formation and maintenance. This review will therefore touch on the importance of Wnt signaling to neurodevelopment generally, while focusing on accumulating evidence for a synaptic role of Wnt signaling. These observations will be discussed in the context of current understanding of the neurodevelopmental bases of major psychiatric diseases, spotlighting schizophrenia, bipolar disorder, and autism spectrum disorder. In short, this review will focus on the potential role of synapse formation and maintenance in major psychiatric disorders and summarize evidence that defective Wnt signaling could contribute to their pathogenesis via effects on these late neural differentiation processes

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky