2,006 research outputs found
MacMahon's sum-of-divisors functions, Chebyshev polynomials, and Quasi-modular forms
We investigate a relationship between MacMahon's generalized sum-of-divisors
functions and Chebyshev polynomials of the first kind. This determines a
recurrence relation to compute these functions, as well as proving a conjecture
of MacMahon about their general form by relating them to quasi-modular forms.
These functions arise as solutions to a curve-counting problem on Abelian
surfaces.Comment: 6 Page
The Long-Term Cost to the UK NHS and Social Services of Different Durations of IV Thiamine (Vitamin B1) for Chronic Alcohol Misusers with Symptoms of Wernicke's Encephalopathy Presenting at the Emergency Department.
BACKGROUND: Wernicke's encephalopathy (WE) is an acute neuropsychiatric condition caused by depleted intracellular thiamine, most commonly arising in chronic alcohol misusers, who may present to emergency departments (EDs) for a variety of reasons. Guidelines recommend a minimum 5-day course of intravenous (IV) thiamine in at-risk patients unless WE can be excluded. OBJECTIVE: To estimate the cost impact on the UK public sector (NHS and social services) of a 5-day course of IV thiamine, vs a 2- and 10-day course, in harmful or dependent drinkers presenting to EDs. METHODS: A Markov chain model compared expected prognosis of patients under alternative admission strategies over 35 years. Model inputs were derived from a prospective cohort study, expert opinion via structured elicitation and NHS costing databases. Costs (2012/2013 price year) were discounted at 3.5 %. RESULTS: Increasing treatment from 2 to 5 days increased acute care costs but reduced the probability of disease progression and thus reduced the expected net costs by GBP87,000 per patient (95 % confidence interval GBP19,300 to GBP172,300) over 35 years. CONCLUSIONS: Increasing length of stay to optimize IV thiamine replacement will place additional strain on acute care but has potential UK public sector cost savings. Social services and the NHS should explore collaborations to realise both the health benefits to patients and savings to the public purse.This study was funded by Archimedes UK Pharma Ltd, the manufacturer of Pabrinex®. Hayward Medical Communications provided editorial and writing support during manuscript development.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s40258-015-0214-
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Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1
Reversible phase separation, which underpins the role of FUS in ribonucleoprotein granules and other membrane-free organelles, is in part driven by the intrinsically disordered low complexity (LC) domain of FUS. Here, we report that cooperative cation-π interactions between tyrosines in the LC domain and arginines in structured C-terminal domains also contribute to phase separation. These interactions are modulated by post-translational arginine methylation, wherein arginine hypomethylation strongly promotes phase separation and gelation. Indeed, significant hypomethylation, which occurs in FUS-associated frontotemporal lobar degeneration, induces FUS condensation into stable intermolecular β-sheet-rich hydrogels that disrupt RNP granule function and impair new protein synthesis in neuron terminals. We show that transportin acts as a physiological molecular chaperone of FUS in neuron terminals, reducing phase separation and gelation of methylated and hypomethylated FUS, and rescuing protein synthesis. These results demonstrate how FUS condensation is physiologically regulated, and how perturbations in these mechanisms can lead to disease
Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?
A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. © 2013 Capra et al
Management of a South African family with retinitis pigmentosa—should potential therapy influence translational research protocols?
Mutation analysis of retinal candidate genes is performed as part of an ongoing research to identify the causative genetic defect in South African families with retinal degenerative disorders (RDDs). A translational research protocol has been established whereby probands are counseled and given their molecular genetic results to take back to other family members, who can then request individual diagnostic testing. A Thr17Met mutation of the rhodopsin gene was identified in a Caucasian South African family with autosomal dominant retinitis pigmentosa. Patients with this mutation appear to benefit from treatment using oral vitamin A supplementation. This family has been informed that a molecular diagnosis is available; however, one individual has refused testing and none of the younger generation has shown interest in receiving molecular results or genetic counseling. Adapting the established protocol for the translation of RDD research results and contacting mutation positive individuals may be justifiable in light of the potential benefit of therapy
The Acute Impact of Changes to Haemodynamic Load on the Left Ventricular Strain-Volume Relationship in Young and Older Men.
OBJECTIVES: Chronic changes in left ventricular (LV) haemodynamics, for example induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof-of-concept that: 1. the LV longitudinal strain (ԑ)-volume loop is sensitive to detect an acute increase in afterload, and 2. these effects differ between healthy young versus older men. METHODS: Thirty-five healthy male volunteers were recruited including 19 young (24±2 yr) and 16 older participants (67±5 yr). Tests were performed prior to, during and after 10-min recovery from acute manipulation of afterload. Real-time haemodynamic data was obtained and LV longitudinal ԑ-volume loops were calculated from 4-chamber images using 2D-echocardiography. RESULTS: Inflation of the anti-G-suit resulted in an immediate increase in heart rate, blood pressure and systemic vascular resistance, and a decrease in stroke volume (all P0.05). Manipulation of cardiac haemodynamics caused comparable effects in young versus older men (all P>0.05). CONCLUSIONS: Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ԑ-volume loop in young and older men. This supports the potency of the LV longitudinal ԑ-volume loop to provide novel insights into dynamic cardiac function in humans in vivo
Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder
By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups
Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study
<p>Abstract</p> <p>Background</p> <p>Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients.</p> <p>Methods</p> <p>All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D).</p> <p>Results</p> <p>Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (<it>P </it>= 0.027), tumor localization (<it>P </it>= 0.019), and type of therapy (<it>P </it>= 0.005), respectively, in univariate analysis. Treatment modality (<it>P </it>= 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (<it>P </it>< 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (<it>P </it>= 0.069 and <it>P </it>= 0.059, respectively).</p> <p>Conclusions</p> <p>The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.</p
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