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In this paper, we are concerned with the representation of large positive integers as the sum of a fixed number of prime numbers taken from Beatty sequences. We are able to avoid any conditions on the Beatty sequences that they be of finite type which have been required hitherto. We use a form of the Hardy–Littlewood–Vinogradov method, but the proofs are quite delicate.

Long chain omega-3 polyunsaturated fatty acids (LC n -3 PUFA) particularly, eicosapentaenoic acid (EPA, 22: 5 n -3) and docosahexaenoic acid (DHA, 22: 6 n -3) have been reported to reduce the risks of cardiovascular disease (CVD) including myocardial infarction, stroke, coronary artery disease and sudden cardiac death. In addition, these fatty acids play an important role in reduction of cancer risks, Alzheimer's disease, depression and schizophrenia. Furthermore, studies also showed that EPA and DHA are important for foetal development, particularly neuronal and retinal functions. Several recent human trials have strengthened the evidence that EPA and DHA can reduce the risks of various chronic diseases although this has not been a uniform finding. In general, the high prevalence of mortality caused by chronic disease can be prevented by consumption of LC n -3 PUFA, which has been proven to have considerable health benefits. The aim of this paper was to review main scientific evidence regarding the health impact of LC n -3 PUFA, especially EPA and DHA on chronic disease including CVD, cancer, mental health, arthritis and infant development.

Background: To improve access to screening, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was developed through the Centers for Disease Control and Prevention (CDC) to provide low-income, and uninsured underserved women access to timely breast and cervical cancer screening and diagnostic services. This population-based study investigates the demographics and diagnostic outcomes of women who underwent breast cancer screening through this program established at an urban university cancer center compared to data obtained from the national program database. Methods: The Kimmel Cancer Center at Jefferson (KCC) launched its screening program with resources from the CDC, the State of Pennsylvania, and the Susan G. Komen Foundation in 2008. The core of the program is staff lead by a Social Worker/Navigator who connects patients to education and screening services, institutional information and guidance, and follow-up to minimize barriers to access, lessen dropout, and ensure follow-through for timely diagnosis and treatment. Working with our Community-Based partner organizations, uninsured and underinsured women in Philadelphia are able to seamlessly travel from education and screening through to treatment and support. All KCC patients evaluated through this program from 2008–2011 were included and records of the NBCCDP database 2006–2010 for this study and analyses. Results: KCC has a substantially larger African American (54.44% vs. 13.8%), smaller Hispanic (8.59% vs. 27.6%), larger percentage of abnormal mammograms (25.96% vs. 14%), higher breast cancer diagnosed per mammogram (2.13 vs 1.0) and a much younger population than the national cohort. Fewer than 1% of KCC patients have been lost to follow-up. Conclusions: The KCC Breast and Cervical Screening and Treatment Program Services reaches a highly vulnerable and at-risk population, has a higher abnormal mammogram and breast cancer detection rate, and a higher continued participation rate than the national cohort. The Social/Worker/Navigator has a distinct role in providing follow-up for abnormal findings to minimize no-shows by providing creative problem-solving, support, counseling, finding resources to minimize barriers, and contributes significantly to the ease of operation and the continued participation of patients in the program. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-03.

Microtubules tether centrosomes together during interphase. How this is accomplished and what benefit it provides to the cell is not known. We have identified a bipolar, minus-end-directed kinesin, Kif25, that suppresses centrosome separation. Kif25 is required to prevent premature centrosome separation during interphase. We show that premature centrosome separation leads to microtubule-dependent nuclear translocation, culminating in eccentric nuclear positioning that disrupts the cortical spindle positioning machinery. The activity of Kif25 during interphase is required to maintain a centred nucleus to ensure the spindle is stably oriented at the onset of mitosis.

In 1742, Goldbach and Euler in conversation and in an exchange of letters discussed the representation of numbers as sums of at most three primes. Although the question as to whether every even number is the sum of one or two primes (the binary Goldbach conjecture) is still unresolved, this and associated questions have attracted many mathematicians over the years, and have lead to a range of powerful techniques with many applications. This article is a commentary on the historical developments, the underlying key ideas and their widespread influence on a variety of central questions.

In most cases of frontal sinus disease, endoscopic approaches are favored; however, in some situations where an endoscopic approach is insufficient, an “above and below” approach may be suitable, serving as an alternative to more invasive procedures

Many forms of cancer present with a complex metabolic profile characterised by loss of lean body mass known as cancer cachexia. The physical impact of cachexia contributes to decreased patient quality of life, treatment success and survival due to gross alterations in protein metabolism, increased oxidative stress and systemic inflammation. The psychological impact also contributes to decreased quality of life for both patients and their families. Combination therapies that target multiple pathways, such as eicosapentaenoic acid administered in combination with exercise, appetite stimulants, antioxidants or anti-inflammatories, have potential in the treatment of this complex syndrome and require further development.

Understanding how the hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) interacts with nascent RNA would provide valuable insight into the virus's mechanism for RNA synthesis. Using a peptide mass fingerprinting method and affinity capture of peptides reversibly cross-linked to an alkyn-labeled nascent RNA, we identified a region below the Δ1 loop in the fingers domain of the HCV RdRp that contacts the nascent RNA. A modification protection assay was used to confirm the assignment. Several mutations within the putative nascent RNA binding region were generated and analyzed for RNA synthesis in vitro and in the HCV subgenomic replicon. All mutations tested within this region showed a decrease in primer-dependent RNA synthesis and decreased stabilization of the ternary complex. The results from this study advance our understanding of the structure and function of the HCV RdRp and the requirements for HCV RNA synthesis. In addition, a model of nascent RNA interaction is compared with results from structural studies.

Objectives. This paper focuses on current diagnostic and treatment options for Eosinophilic Esophagitis (EE).Study Design. literature review.Results. EE can be suspected on history and endoscopy although definitive diagnosis is strictly based on histopathology. It is a relatively new entity and is often misdiagnosed as gastroesophageal reflux (GERD). Eosinophilic infiltration of the esophageal mucosa is responsible for esophageal symptoms which can range from mild to debilitating dysphagia and food impaction, when untreated. In fact recurrent foreign body and food impaction can often be blamed for undiagnosed EE. There seems to be a strong familial component and association with allergy. The introduction of transnasal esophagoscopy in adult laryngology has enabled otolaryngologists to readily diagnose EE and promoted awareness of this often difficult to recognize entity.Conclusions. Despite higher awareness, the literature suggests that EE remains a commonly misdiagnosed condition especially in the otolaryngology community. Genetic studies are required to unfold the true familial and genetic component of this fascinating entity.

One approach to super-resolution fluorescence imaging uses sequential activation and localization of individual fluorophores to achieve high spatial resolution. Essential to this technique is the choice of fluorescent probes — the properties of the probes, including photons per switching event, on/off duty cycle, photostability, and number of switching cycles, largely dictate the quality of super-resolution images. While many probes have been reported, a systematic characterization of the properties of these probes and their impact on super-resolution image quality has been described in only a few cases. Here, we quantitatively characterized the switching properties of 26 organic dyes and directly related these properties to the quality of super-resolution images. This analysis provides a set of guidelines for characterization of super-resolution probes and a resource for selecting probes based on performance. Our evaluation identified several photoswitchable dyes with good to excellent performance in four independent spectral ranges, with which we demonstrated low crosstalk, four-color super-resolution imaging.

In this paper, we establish two mean value theorems for the number of solutions of the Diophantine equation $\frac{a}{n}=\frac{1}{x}+\frac{1}{y}$, in the case when $a$ is fixed and $n$ varies and in the case when both $a$ and $n$ vary., Comment: 16 pages, to appear in J. Number Theory

Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. To assess the prevalence of persisting lipid abnormalities in patients treated with statins. DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were ≥45 years and treated with statins for ≥3 months. Data were collected from the patients’ records. ESC guidelines were used to classify risk and to define lipid levels. Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk ≥5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score

The above photo of David M. McDowell, MD, was taken just 10 weeks before his death and captures his attitude and approach to life. He stands with his brother Tom atop Machu Picchu with a huge smile...

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) exhibits a preference for G/U-rich RNA in vitro . Biological analysis of the NS5A RNA-binding activity and its target sites in the genome will be facilitated by a description of the NS5A-RNA complex. We demonstrate that the C-4 carbonyl of the uracil base and, by inference, the C-6 carbonyl of the guanine base interact with NS5A. U-rich RNA of 5 to 6 nucleotides (nt) is sufficient for high-affinity binding to NS5A. The minimal RNA-binding domain of NS5A consists of residues 2005 to 2221 (referred to as domain I-plus). This region of the protein includes the amino-terminal domain I as well as the subsequent linker that separates domains I and II. This linker region is the site of adaptive mutations. U-rich RNA-binding activity is not observed for an NS5A derivative containing only residues 2194 to 2419 (domains II and III). Mass spectrometric analysis of an NS5A-poly(rU) complex identified domains I and II as sites for interaction with RNA. Dimerization of NS5A was demonstrated by glutaraldehyde cross-linking. This dimerization is likely mediated by domain I-plus, as dimers of this protein are trapped by cross-linking. Dimers of the domain II-III protein are not observed. The monomer-dimer equilibrium of NS5A shifts in favor of dimer when U-rich RNA is present but not when A-rich RNA is present, consistent with an NS5A dimer being the RNA-binding-competent form of the protein. These data provide a molecular perspective of the NS5A-RNA complex and suggest possible mechanisms for regulation of HCV and cellular gene expression.

There is a significant body of evidence showing that patients want to know when they are harmed as a result of their medical care. In 2005 the National Patient Safety Agency issued guidance on the process to be followed when communicating errors to patients and their carers. However, there is still a significant gap between the rhetoric of being open and clinical practice. This gap reflects the competing interests arising from the concept of being open and the difficulties involved in the process itself. This paper presents several case studies to explore the complexities of being open and the organizational support required to overcome these.

This article is reprinted by kind permission of Veterinary History where it first appeared in Vol. 14, No. 2 (2008), pgs. 119–136. The paper is the text of an invited lecture that was given by the late Professor Leslie Vaughan. It has not been peer-reviewed, but is reprinted for readers of VCOT. An obituary to Professor Vaughan was published in VCOT 2009 22(3): IX-X.

Viral capsid proteins (CPs) can regulate gene expression and encapsulate viral RNAs. Low-level expression of the brome mosaic virus (BMV) CP was found to stimulate viral RNA accumulation, while higher levels inhibited translation and BMV RNA replication. Regulation of translation acts through an RNA element named the B box, which is also critical for the replicase assembly. The BMV CP has also been shown to preferentially bind to an RNA element named SLC that contains the core promoter for genomic minus-strand RNA synthesis. To further elucidate CP interaction with RNA, Available online we used a reversible cross-linking–peptide fingerprinting assay to identify 27 May 2009 peptides in the capsid that contact the SLC, the B-box RNA, and the encapsidated RNA. Transient expression of three mutations made in residues within or close by the cross-linked peptides partially released the normal inhibition of viral RNA accumulation in agroinfiltrated Nicotiana benthamiana. Interestingly, two of the mutants, R142A and D148A, were found to retain the ability to down-regulate reporter RNA translation. These two mutants formed viral particles in inoculated leaves, but only R142Awas able to move systemically in the inoculated plant. The R142A CP was found to have higher affinities for SLC and the B box compared with those of wild-type CP and to alter contacts to the RNA in the virion. These results better define how the BMV CP can interact with RNA and regulate different viral processes.

Cytoplasmic RNA receptors are important in the detection of and response to viral infections. We analyzed ligand recognition by the retinoic acid-inducible protein I (RIG-I) protein in biochemical assays and in transiently transfected cells and characterized the requirements for both single- and double-stranded RNA agonists for RIG-I activation of signaling. RIG-I mutants such as K270A and T409A/S411A that were defective in signaling with triphosphorylated single-stranded RNAs were perfectly capable of signaling with dsRNAs. Furthermore, phosphorothioated oligodeoxynucleotides were found to antagonize RIG-I signaling. Both agonists and antagonist bind purified RIG-I protein and a truncated RIG-I protein that lacked the signaling domain. The agonists were necessary to activate RIG-I ATPase activity in vitro, whereas antagonist inhibited ATPase activity. Differential scanning fluorometry showed that RIG-I bound to agonists, and antagonists have different denaturation properties, suggesting a difference in protein conformations. Last, single particle reconstruction was used to generate three-dimensional models of the RIG-I dimers in complex with an agonist and an antagonist. The two complexes exhibited dramatically different structures.

On May 1, 2004, the Association of Gay and Lesbian Psychiatrists (AGLP), with co-sponsorship from St. Luke's–Roosevelt Medical Center, The Haworth Press, and the William Alanson White Institute, organized an all-day conference in New York City entitled Homosexuality and Psychoanalysis: New Directions. The proceedings of the third panel focused on “Theoretical Perspectives.” The first panelist, Susan C. Vaughan, MD, discusses how her perspective on lesbian development affects her clinical work with patients. Vaughan believes that the most useful framework for understanding the psychological ramifications of being lesbian is a developmental perspective, by which she means what is experiential about development and appreciating cultural factors, as well as what they might mean intrapsychically to patients as they are going through their lives growing up lesbian. Vaughan presents detailed clinical case material to highlight three developmental themes that are common in the lesbian patients that she h...

This study surveyed 181 parents of students enrolled in one of two early entrance programs at the University of Washington: the Early Entrance Program for students who entered before age 15 and the University of Washington Academy for Young Scholars for students who matriculated after Grade 10. The purpose was to understand parents' perspectives on the early entrance experience, including reasons for choosing early entrance, satisfaction with their children's program, perceived advantages and disadvantages of early entrance, and the effect of early entrance on family relationships. Ninety-five parents participated, with the majority reporting great satisfaction with multiple aspects of their and their children's experience. Early Entrance Program parents expressed a slightly higher degree of satisfaction than did Academy parents. This study suggests that early university entrance is an attractive option for parents willing to follow the lead of their talented and ambitious adolescents. Putting the Research to Use: Early entrance programs are attractive options for parents of academically advanced students who have outpaced available secondary programs. These programs are not inevitably initially successful; however, as our study demonstrates, they benefit greatly from ongoing program evaluation and analysis. Key components of effective early entrance programs include intensive advising, community building, thoughtful selection of students, active engagement by students and faculty, and a welcoming college or university environment. Careful attention to the informational needs of parents is also important, particularly about the social and emotional transitions that they and their children are likely to experience. The University of Washington has demonstrated with two programs that early university entrance is prized by students, parents, university officials, and state education agencies. These and similar programs might well be replicated in other areas around the country given active partnerships among all concerned parties.

Toll-like receptor 3 (TLR3) can signal the production of a suite of cytokines and chemokines in response to double-stranded RNA (dsRNA) ligands or the dsRNA mimic poly(I-C). Using a human embryonic kidney 293T cell line to express human TLR3, we determined that poly(I-C)-induced signal could be significantly inhibited by single-stranded DNAs (ssDNAs), but not ssRNA or dsDNA. The ssDNA molecules that down-modulated TLR3 signaling did not affect TLR4 and do not require the hypomethylated CpG motif found in TLR9 ligands. The degree of modulation can be altered by the length, base sequence, and modification state of the ssDNAs. An inhibitory ssDNA was found to colocalize with TLR3 in transfected cells and in a cell line that naturally expresses TLR3. The inhibitory ssDNAs can compete efficiently with dsRNA for binding purified TLR3 ectodomains in vitro, while noninhibitory nucleic acids do not. The ssDNAs also decrease the levels of several cytokines produced by the human bronchial epithelial cell line BEAS-2B and by human peripheral blood mononuclear cells in response to poly(I-C) stimulation of native TLR3. These activities indicate that ssDNAs could be used to regulate the inflammatory response through TLR3.

Anesthetic management during functional endoscopic sinus surgery is aimed at minimizing bleeding and establishing a near-perfect surgical field. We investigated whether deliberate intraoperative hypercapnia and hypocapnia may affect blood loss and quality of surgical field through a proposed modulating effect of different carbon dioxide (CO2) tension levels on nasal vasculature.One hundred and eighty patients were randomly assigned to normocapnia (end-tidal CO2 [ETco2] 37 +/- 2 mm Hg), hypercapnia (ETco2 60 +/- 2 mm Hg), and hypocapnia (ETco2 27 +/- 2 mm Hg) groups. Anesthetic management was with propofol and remifentanil infusions, nitrous oxide, and moderate controlled hypotension. Blood loss and operating conditions were assessed by the surgeon who was blinded to group assignment. Differences among the study groups, the effect of the study group and time on ETco2 levels and hemodynamic variables, and the association of blood loss with surgical covariates were analyzed.There were no differences in blood loss and quality of surgical field among the study groups. Patients in the hypocapnia group demonstrated the highest, and in the hypercapnia group, the lowest, requirements for remifentanil, labetalol, and administration of the antihypertensive medications in general. The computed tomography-graded severity of sinonasal disease and duration of surgery were the only independent predictors of intraoperative blood loss.CO2 management during functional endoscopic sinus surgery does not influence operating conditions or blood loss.

There is, apparently, a persistent belief that in the current state of knowledge it is not possible to obtain an asymptotic formula for the number of partitions of a number n into primes when n is large. In this paper such a formula is obtained. Since the distribution of primes can only be described accurately by the use of the logarithmic integral and a sum over zeros of the Riemann zeta-function one cannot expect the main term to involve only elementary functions. However the formula obtained, when n is replaced by a real variable, is in ${\mathcal{C}}^{\infty}$ and is readily seen to be monotonic.

Let me begin by explaining the origins of the title of my talk today. Back in 1997, when my partner and I were proposing to our own Ob-gyn, an infertility specialist, our plan for me to become preg...

Let C be a nondegenerate planar curve and for a real, positive decreasing function ψ let C(ψ) denote the set of simultaneously ψ-approximable points lying on C. We show that C is of Khintchine type for divergence; i.e. if a certain sum diverges then the one-dimensional Lebesgue measure on C of C(ψ) is full. We also obtain the Hausdorff measure analogue of the divergent Khintchine type result. In the case that C is a rational quadric the convergence counterparts of the divergent results are also obtained. Furthermore, for functions ψ with lower order in a critical range we determine a general, exact formula for the Hausdorff dimension of C(ψ). These results constitute the first precise and general results in the theory of simultaneous Diophantine approximation on manifolds.

Between electronics and photonics there exists a frequency gap of approximately two octaves, i.e., the frequency range between 100 GHz and 10 THz, across which there are limited capabilities for signal generation, control, guidance, and processing. Here, we demonstrate that phonon-polaritons in ionic crystals like LiNbO3 or LiTaO3 may be used to bridge this gap. The ability to directly visualize polariton fields through real-space imaging, to generate arbitrary THz waveforms through the use of temporally and/or spatially shaped optical waveforms, and to fabricate integrated functional elements for polariton guidance and control through laser machining yields a THz polaritonics platform that enables advanced signal processing and spectroscopy applications.

OBJECTIVE: The aim of this study was to further evaluate the safety and effectiveness of balloon catheter devices to dilate obstructed sinus ostia/perform sinusotomy. METHODS: Through a prospective, multicenter evaluation, safety was assessed by rate of adverse events, patency was determined by endoscopic examination, and sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT 20). RESULTS: At the conclusion of the 24-week analysis, endoscopy determined that the sinusotomy was patent in 80.5% (247 of 307) sinuses and nonpatent in 1.6% (5 of 307), and could not determine ostial patency status in 17.9% (55 of 307). Of the ostia visualized on endoscopy, 98% were patent (247 of 252), while 2% (5 of 252) were considered nonpatent. SNOT 20 scores showed consistent symptomatic improvement over baseline. Revision treatment was required in 3 sinuses (3 of 307 sinuses, 0.98%) in 3 patients (3 of 109 patients, 2.75%). CONCLUSION: Balloon catheter technology appears safe and effective in relieving ostial obstruction. Patients were pleased and indicated that they experienced symptomatic improvement.

This is the second follow-up study of the Early Entrance Program at the University of Washington. Ninety-five individuals (45%) participated. Respondents overwhelmingly chose early university entrance because they were excited to learn; many also praised the peer group, intellectual stimulation, and faculty and staff support. Some reported feeling too young to make important academic, career, and social decisions, with more males regretting the lack of dating partners because of age differences. As the program has matured, so have students' positive experiences in it. Significant differences were found among three groups of students who entered at different points, reflecting this maturation. A wealth of open-ended comments indicated that the program continues to exert a profound and positive influence on graduates' lives.

Single-molecule, localization-based, super resolution microscopy is able to reveal detailed subcellular structures and protein distributions below the classical ∼250-nm diffraction limit of light, but utilizing this technique effectively requires a combination of careful sample preparation, data acquisition, and data analysis, which can be daunting to novice researchers. In this protocol, detailed instructions on preparation of robust reference samples for super-resolution microscopy, including the cytoskeleton (microtubules), membrane-bound organelles (peroxisomes), and scaffold proteins (clathrin), are provided. These samples also constitute a representative subset of imaging targets of interest to biological researchers and highlight the differences and similarities in sample preparation.

RNA nanotechnology often feature protein RNA complexes. The interaction between proteins and large RNAs are difficult to study using traditional structure-based methods like NMR or X-ray crystallography. RCAP, an approach that uses reversible-cross-linking affinity purification method coupled with mass spectrometry, has been developed to map regions within proteins that contact RNA. This chapter details how RCAP is applied to map protein-RNA contacts within virions.

Studies suggest an independent association between Obstructive Sleep Apnoea Syndrome (OSAS) and cardiovascular death. The purpose of our study is to examine doctors' awareness of this association and to determine whether this correlates with recording of OSAS on death certificates. We contacted the Central Statistics Office (CSO) and obtained relevant mention of OSAS on death certificates. We surveyed doctors on their view of OSAS-related deaths, CSO data from 2008-2011 reveal two deaths with OSAS documented as a direct cause and 52 deaths with OSAS as a contributory cause. Seventy-five doctors' surveyed (41%) believe OSAS can be a direct cause of death and 177 (96%) believe OSAS can be an indirect cause of death. Only 22 (12%) had putdown OSAS as a cause of death. OSAS is seldom recorded on death certificates. This is at odds with epidemiological forecasts and contrary to an opinion poll from a selection of doctors.

RNA nanotechnology often feature protein RNA complexes. The interaction between proteins and large RNAs are difficult to study using traditional structure-based methods like NMR or X-ray crystallography. RCAP, an approach that uses reversible-cross-linking affinity purification method coupled with mass spectrometry, has been developed to map regions within proteins that contact RNA. This chapter details how RCAP is applied to map protein-RNA contacts within virions.

Objective To compare venous ulcer recurrence and compliance with two strengths of compression hosiery. Methods This study was a randomized controlled trial with a 5-year follow-up. The setting was the leg ulcer clinics of a teaching and a district general hospital in Scotland, United Kingdom. Patients were 300 outpatients with recently healed venous ulcers, with no significant arterial disease, rheumatoid disease, or diabetes mellitus. Interventions were fitting and supply of class 2 or class 3 compression hosiery. Four-monthly refitting by trained orthotists and surveillance by specialist nurses were performed. The main outcome measures were recurrence of leg ulceration and compliance with treatment. Results Thirty-six percent (107/300) of patients had recurrent leg ulceration by 5 years. Recurrence occurred in 59 (39%) of 151 class 2 elastic compression cases and in 48 (32%) of class 3 compression cases. One hundred six patients did not comply with their randomized compression class, 63 (42%) in class 3 and 43 (28%) in class 2. The difference in recurrence is not statistically significant, but our estimate of the effectiveness of class 3 hosiery is diluted by the lower compliance rate in this group. Restricted ankle movement and four or more previous ulcers were associated with a higher risk of recurrence. Conclusions There was no evidence of a difference in recurrence rates at the classic level of significance (5%), but the lowest recurrence rates were seen in people who wore the highest degree of compression. Therefore, patients should wear the highest level of compression that is comfortable.