A Case Report of Incidental Primary Leiomyosarcoma of the Fallopian Tube and a Review of the Recent Literature

Primary leiomyosarcoma of the fallopian tube is a very rare neoplasm with descriptions limited to case reports. We present the case of a 46-yr-old woman with a history of renal transplantation in whom a primary leiomyosarcoma of the fallopian tube was identified incidentally following hysterectomy and bilateral salpingectomy undertaken for a uterine fibroid. The tumor demonstrated classic morphological and immunohistochemical features of a leiomyosarcoma. It appeared localized to the fallopian tube and was completely resected. Adjuvant therapy was not given but active surveillance initiated. After 14 mo of follow-up, there was no evidence of disease recurrence. We review cases from the past 20 yr with a focus on management and outcomes. Given the rarity of this disease, continued publication of case reports and the creation of a centralized case registry would be of benefit

Where do we go from here? An assessment of navigation performance using a compass versus a GPS unit

The Global Positioning System (GPS) looks set to replace the traditional map and compass for navigation tasks in military and civil domains. However, we may ask whether GPS has a real performance advantage over traditional methods. We present an exploratory study using a waypoint plotting task to compare the standard magnetic compass against a military GPS unit, for both expert and non-expert navigators. Whilst performance times were generally longer in setting up the GPS unit, once navigation was underway the GPS was more efficient than the compass. For mediumto long-term missions, this means that GPS could offer significant performance benefits, although the compass remains superior for shorter missions. Notwithstanding the performance times, significantly more errors, and more serious errors, occurred when using the compass. Overall, then, the GPS offers some clear advantages, especially for non-expert users. Nonetheless, concerns over the development of cognitive maps remain when using GPS technologies

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles

The Graded Incomplete Letters Test (GILT): a rapid test to detect cortical visual loss, with UK Biobank implementation

Impairments of object recognition are core features of neurodegenerative syndromes, in particular posterior cortical atrophy (PCA; the ‘visual-variant Alzheimer’s disease’). These impairments arise from damage to higher-level cortical visual regions and are often missed or misattributed to common ophthalmological conditions. Consequently, diagnosis can be delayed for years with considerable implications for patients. We report a new test for the rapid measurement of cortical visual loss – the Graded Incomplete Letters Test (GILT). The GILT is an optimised psychophysical variation of a test used to diagnose cortical visual impairment, which measures thresholds for recognising letters under levels of increasing visual degradation (decreasing "completeness") in a similar fashion to ophthalmic tests. The GILT was administered to UK Biobank participants (total n=2,359) and participants with neurodegenerative conditions characterised by initial cortical visual (PCA, n=18) or memory loss (typical Alzheimer’s disease, n=9). UK Biobank participants, including both typical adults and those with ophthalmological conditions, were able to recognise letters under low levels of completeness. In contrast, participants with PCA consistently made errors with only modest decreases in completeness. GILT sensitivity to PCA was 83.3% for participants reaching the 80% accuracy cut-off, increasing to 88.9% using alternative cut-offs (60% or 100% accuracy). Specificity values were consistently over 94% when compared to UK Biobank participants without or with documented visual conditions, regardless of accuracy cut-off. These first-release UK Biobank and clinical verification data suggest the GILT has utility in both rapidly detecting visual perceptual losses following posterior cortical damage and differentiating perceptual losses from common eye-related conditions

Charge 4e4e superconductivity from pair density wave order in certain high temperature superconductors

A number of spectacular experimental anomalies\cite{li-2007,fujita-2005} have recently been discovered in certain cuprates, notably {\LBCO} and {\LNSCO}, which exhibit unidirectional spin and charge order (known as ``stripe order''). We have recently proposed to interpret these observations as evidence for a novel ``striped superconducting'' state, in which the superconducting order parameter is modulated in space, such that its average is precisely zero. Here, we show that thermal melting of the striped superconducting state can lead to a number of unusual phases, of which the most novel is a charge $4e$ superconducting state, with a corresponding fractional flux quantum $hc/4e$. These are never-before observed states of matter, and ones, moreover, that cannot arise from the conventional Bardeen-Cooper-Schrieffer (BCS) mechanism. Thus, direct confirmation of their existence, even in a small subset of the cuprates, could have much broader implications for our understanding of high temperature superconductivity. We propose experiments to observe fractional flux quantization, which thereby could confirm the existence of these states.Comment: 5 pages, 2 figures; new version in Nature Physics format with a discussion of the effective Josephson coupling J2 and minor changes. Mildly edited abstract. v3: corrected versio

New evidence on Allyn Young's style and influence as a teacher

This paper publishes the hitherto unpublished correspondence between Allyn Abbott Young's biographer Charles Blitch and 17 of Young's former students or associates. Together with related biographical and archival material, the paper shows the way in which this adds to our knowledge of Young's considerable influence as a teacher upon some of the twentieth century's greatest economists. The correspondents are as follows: James W Angell, Colin Clark, Arthur H Cole, Lauchlin Currie, Melvin G de Chazeau, Eleanor Lansing Dulles, Howard S Ellis, Frank W Fetter, Earl J Hamilton, Seymour S Harris, Richard S Howey, Nicholas Kaldor, Melvin M Knight, Bertil Ohlin, Geoffrey Shepherd, Overton H Taylor, and Gilbert Walker

High-efficiency Rosa26 knock-in vector construction for Cre-regulated overexpression and RNAi

Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction = 9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when similar to 1150 subjects experience a primary endpoint

Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study

Background Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change. Methods Using national data from Hospital Episode Statistics covering 1998–2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date. Results Infective endocarditis incidence increased markedly over the study (22.2–41.3 per million population in 1998 to 42.0–67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000–May 2003) to May 2015 (March 1999–January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006–April 2010) to August 2015 (September 2013–November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date. Conclusions Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase

Fine mapping of candidate effector genes for heart rate

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality

Criticality in correlated quantum matter

At quantum critical points (QCP) \cite{Pfeuty:1971,Young:1975,Hertz:1976,Chakravarty:1989,Millis:1993,Chubukov:1 994,Coleman:2005} there are quantum fluctuations on all length scales, from microscopic to macroscopic lengths, which, remarkably, can be observed at finite temperatures, the regime to which all experiments are necessarily confined. A fundamental question is how high in temperature can the effects of quantum criticality persist? That is, can physical observables be described in terms of universal scaling functions originating from the QCPs? Here we answer these questions by examining exact solutions of models of correlated systems and find that the temperature can be surprisingly high. As a powerful illustration of quantum criticality, we predict that the zero temperature superfluid density, $\rho_{s}(0)$, and the transition temperature, $T_{c}$, of the cuprates are related by $T_{c}\propto\rho_{s}(0)^y$, where the exponent $y$ is different at the two edges of the superconducting dome, signifying the respective QCPs. This relationship can be tested in high quality crystals.Comment: Final accepted version not including minor stylistic correction