PCR and Mosquito dissection as tools to monitor filarial infection levels following mass treatment

BACKGROUND: Entomological methods may provide important tools for monitoring the progress of lymphatic filariasis elimination programs. In this study, we compared dissection of the vector, Culex quinquefasciatus, with the polymerase chain reaction (PCR) to assess filarial infection levels in mosquitoes in the context of a lymphatic filariasis elimination program in Leogane, Haiti. METHODS: Mosquitoes were collected using gravid traps located in 4 sentinel communities with Wuchereria bancrofti microfilaria prevalence that ranged from 0.8% to 15.9%. Captured mosquitoes were divided between dissection, to enumerate W. bancrofti larvae (L1, L2, L3) and desiccation for later analysis by PCR. PCR was conducted on DNA extracts from pooled mosquitoes (1–15 pooled females) utilizing a competitive PCR system with primers specific for the Ssp I repeat. PCR products were analyzed with a hybridization ELISA using probes specific for a control sequence and the Ssp I repeat. RESULTS: The prevalence of mosquito infection with W. bancrofti ranged from 0%–3.66% by dissection (L1–L3) and point estimates of infection prevalence, as assayed by PCR, ranged from 0.25% – 9.16%. Following mass treatment, W. bancrofti infection prevalence dropped significantly as determined by PCR and dissection in 2 of the 4 sentinel sites (Leogane and Barrier Jeudi, P = 0.04 and P = 0.005, respectively). Although transmission declined in the other two sites, larval recoveries were low and these changes were not statistically significant. DISCUSSION: Our results suggest that a single round of mass treatment can have an impact on transmission of lymphatic filariasis. The use of entomologic methods as a tool to monitor filariasis programs and the statistical limitations of mosquito trapping are discussed

Mitigation of welding distortion and residual stresses via cryogenic CO2 cooling-a numerical investigation

Fusion welding remains the most common and convenient fabrication method for large, thin- plate welded structures. However, the resulting tendency to out-of-plane distortion exacts severe design and fabrication penalties in terms of poorer buckling performance, lack of fairness in external appearance, poor fit-up and frequent requirements for expensive rework. There are several ways to mitigate welding distortion and this study concentrates on the use of cryogenic CO2 cooling to reduce distortion. A feasible combination of welding process and cooling parameters, was investigated computationally and the resulting effects on final deformation were predicted. Three different computational strategies were developed and applied to butt-welding and fillet-welding processes, with and without the inclusion of cryogenic cooling. In the first method, a fully transient, uncoupled thermo-elastoplastic model was investigated. This method is comprehensive but not readily applicable to predict welding distortions in complex, industrial-scale, welded structures, due to the large computational requirement. More computationally efficient models are needed therefore and two further models of this type are suggested in this study. The results show good agreement between the different models, despite substantial differences in computational budget. In butt-welded plates, a significant decrease in out-of-plane distortion is obtained when cryogenic cooling is applied. In fillet-welded plates, cooling had much less effect on welding distortion. This was largely due to the size and configuration of the test case assemblies and the fact that the attached stiffener greatly increased the overall stiffness and resistance to contraction forces.peer-reviewe

The Orbit of the Eclipsing X-ray Pulsar EXO 1722-363

With recent and archival Rossi X-Ray Timing Explorer (RXTE) X-ray measurements of the heavily obscured X-ray pulsar EXO 1722-363 (IGR J17252-3616), we carried out a pulse timing analysis to determine the orbital solution for the first time. The binary system is characterized by a_x sin(i) = 101 +/- 3 lt-s and P_orb = 9.7403 +/- 0.0004 days (90% confidence), with the precision of the orbital period being obtained by connecting datasets separated by more than 7 years (272 orbital cycles). The orbit is consistent with circular, and e < 0.19 at the 90% confidence level. The mass function is 11.7 +/- 1.2 M_sun and confirms that this source is a High Mass X-ray Binary (HMXB) system. The orbital period, along with the previously known ~414 s pulse period, places this system in the part of the Corbet diagram populated by supergiant wind accretors. Using previous eclipse time measurements by Corbet et al. and our orbital solution, combined with the assumption that the primary underfills its Roche lobe, we find i > 61 degrees at the 99% confidence level, the radius of the primary is between 21 R_sun and 37 R_sun, and its mass is less than about 22 M_sun. The acceptable range of radius and mass shows that the primary is probably a supergiant of spectral type B0I-B5I. Photometric measurements of its likely counterpart are consistent with the spectral type and luminosity if the distance to the system is between 5.3 kpc and 8.7 kpc. Spectral analysis of the pulsar as a function of orbital phase reveals an evolution of the hydrogen column density suggestive of dense filaments of gas in the downstream wake of the pulsar, with higher levels of absorption seen at orbital phases 0.5-1.0, as well as a variable Fe K_alpha line.Comment: Submitted to ApJ, 11 pages, 11 figure

Life-threatening acute acalculous cholecystitis in a patient with renal cell carcinoma treated by sunitinib: a case report

<p>Abstract</p> <p>Introduction</p> <p>Sunitinib, an oral multitargeted tyrosine kinase inhibitor, is widely used in the treatment of renal cell carcinoma and gastrointestinal stromal tumor and has had a variety of adverse events. However, sunitinib-related acute cholecystitis has been reported in only two patients with gastrointestinal stromal tumor and renal cell carcinoma (clear cell subtype).</p> <p>Case presentation</p> <p>A 75-year-old Japanese woman with a right sided abdominal swelling was referred to our hospital. Computed tomography (CT) showed a hypervascular bulky tumor in her right kidney, suggesting right renal cell carcinoma in clinical T4N0M0. Although sunitinib therapy was started as neoadjuvant chemotherapy, during the fourth week of the first cycle, she developed acute acalculous cholecystitis and disseminated intravascular coagulation associated with sunitinib. Sunitinib therapy was discontinued immediately and she recovered after subsequent treatment with antibiotics and gabexate mesilate followed by percutaneous cholecystostomy. Cholecystectomy and right radical nephrectomy were performed and pathological examination showed that her renal tumor was a chromophobe renal cell carcinoma (pT2) with necrosis. Inflammation and ischemia were observed in the gallbladder wall, which was compatible with acute acalculous cholecystitis. There has been no evidence of disease recurrence for more than six months.</p> <p>Conclusion</p> <p>We described the third case of sunitinib-related acute cholecystitis in a patient with chromophobe renal cell carcinoma. Attention is required to sunitinib-related acute cholecystitis which, while uncommon, could be life-threatening.</p

Diagnostic accuracy of liquid biopsy in endometrial cancer

Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. Methods: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. Results: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. Conclusions: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted.publishedVersio

The Minimal Phantom Sector of the Standard Model: Higgs Phenomenology and Dirac Leptogenesis

We propose the minimal, lepton-number conserving, SU(3)xSU(2)xU(1) gauge-singlet, or phantom, extension of the Standard Model. The extension is natural in the sense that all couplings are of O(1) or forbidden due to a phantom sector global U(1)_D symmetry, and basically imitates the standard Majorana see-saw mechanism. Spontaneous breaking of the U(1)_D symmetry triggers consistent electroweak gauge symmetry breaking only if it occurs at a scale compatible with small Dirac neutrino masses and baryogenesis through Dirac leptogenesis. Dirac leptogenesis proceeds through the usual out-of-equilibrium decay scenario, leading to left and right-handed neutrino asymmetries that do not fully equilibrate after they are produced. The model contains two physical Higgs bosons and a massless Goldstone boson. The existence of the Goldstone boson suppresses the Higgs to bb branching ratio and instead the Higgs bosons will mainly decay to invisible Goldstone and/or to visible vector boson pairs. In a representative scenario, we estimate that with 30 fb^-1 integrated luminosity, the LHC could discover this invisibly decaying Higgs, with mass ~120 GeV. At the same time a significantly heavier, partner Higgs boson with mass ~210 GeV could be found through its vector boson decays. Electroweak constraints as well as astrophysical and cosmological implications are analysed and discussed.Comment: 21 pages, 4 figures. Corrected typos and added references. To appear in JHE

"They're Really PD Today": An Exploration of Mental Health Nursing Students' Perceptions of Developing a Therapeutic Relationship With Patients With a Diagnosis of Antisocial Personality Disorder

The therapeutic relationship is of particular importance when working with patients with antisocial personality disorder, but despite this, there is a paucity of literature exploring student nurses’ perceptions of developing a therapeutic relationship with such patients. Hence, this qualitative study explored the perceptions of second-year mental health nursing students of developing a therapeutic relationship with this patient group. Student nurses from a University in the Northwest of England participated in two focus groups, to compare the perceptions of a group of student nurses who had experience in secure settings (forensic hospital) with those who had not. Four key themes emerged: diagnosis, safety, engagement, and finally environmental influences. Both groups commented on looking beyond the diagnosis and seeing the person. The student nurses cited other staff in their clinical placement areas as hugely influential in terms of the development of their perceptions of patients with antisocial personality disorder and how to relate to them

Time Course and Mechanism of Myocardial Catecholamine Release During Transient Ischemia In Vivo

BACKGROUND: Elevated concentrations of norepinephrine (NE) have been observed in ischemic myocardium. We investigated the magnitude and mechanism of catecholamine release in the myocardial interstitial fluid (MIF) during ischemia and reperfusion in vivo through the use of microdialysis. METHODS AND RESULTS: In 9 anesthetized pigs, interstitial catecholamine concentrations were measured in the perfusion areas of the left anterior descending coronary artery (LAD) and the left circumflex coronary artery. After stabilization, the LAD was occluded for 60 minutes and reperfused for 150 minutes. During the final 30 minutes, tyramine (154 nmol. kg(-1). min(-1)) was infused into the LAD. During LAD occlusion, MIF NE concentrations in the ischemic region increased progressively from 1. 0+/-0.1 to 524+/-125 nmol/L. MIF concentrations of dopamine and epinephrine rose from 0.4+/-0.1 to 43.9+/-9.5 nmol/L and from <0.2 (detection limit) to 4.7+/-0.7 nmol/L, respectively. Local uptake-1 blockade attenuated release of all 3 catecholamines by >50%. During reperfusion, MIF catecholamine concentrations returned to baseline within 120 minutes. At that time, the tyramine-induced NE release was similar to that seen in nonischemic control animals despite massive infarction. Arterial and MIF catecholamine concentrations in the left circumflex coronary artery region remained unchanged. CONCLUSIONS: Myocardial ischemia is associated with a pronounced increase of MIF catecholamines, which is at least in part mediated by a reversed neuronal reuptake mechanism. The increase of MIF epinephrine implies a (probably neuronal) cardiac source, whereas the preserved catecholamine response to tyramine in postischemic necrotic myocardium indicates functional integrity of sympathetic nerve terminals

Catecholamine handling in the porcine heart: a microdialysis approach

Experimental findings suggest a pronounced concentration gradient of norepinephrine (NE) between the intravascular and interstitial compartments of the heart, compatible with an active neuronal reuptake (U1) and/or an endothelial barrier. Using the microdialysis technique in eight anesthetized pigs, we investigated this NE gradient, both under baseline conditions and during increments in either systemic or myocardial interstitial fluid (MIF) NE concentration. At steady state, baseline MIF NE (0.9 +/- 0.1 nmol/l) was higher than arterial NE (0.3 +/- 0.1 nmol/l) but was not different from coronary venous NE (1.5 +/- 0.3 nmol/l). Local U1 inhibition raised MIF NE concentration to 6.5 +/- 0.9 nmol/l. During intravenous NE infusions (0.6 and 1.8 nmol. kg(-1). min(-1)), the fractional removal of NE by the myocardium was 79 +/- 4% to 69 +/- 3%, depending on the infusion rate. Despite this extensive removal, the quotient of changes in MIF and arterial concentration (DeltaMIF/DeltaA ratio) for NE were only 0.10 +/- 0.02 for the lower infusion rate and 0.11 +/- 0.01 for the higher infusion rate, whereas U1 blockade caused the DeltaMIF/DeltaA ratio to rise to 0.21 +/- 0.03 and 0.36 +/- 0.05, respectively. From the differences in DeltaMIF/DeltaA ratios with and without U1 inhibition, we calculated that 67 +/- 5% of MIF NE is removed by U1. Intracoronary infusion of tyramine (154 nmol. kg(-1). min(-1)) caused a 15-fold increase in MIF NE concentration. This pronounced increase was paralleled by a comparable increase of NE in the coronary vein. We conclude that U1 and extraneuronal uptake, and not an endothelial barrier, are the principal mechanisms underlying the concentration gradient of NE between the interstitial and intravascular compartments in the porcine heart