Publications by authors named "RJ Manning"

Current guidelines recommend a seven-day course of antibiotic therapy for patients with ventilator-associated pneumonia (VAP). However, clinical and microbiologic resolution of infection may occur much sooner than seven days, particularly in patients with early VAP. Shortening the course of antibiotic therapy for early VAP likely results in lower antibiotic-associated complications, but it is unclear whether VAP recurrence rates will be higher in patients receiving fewer days of therapy.

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  • MYD88 mutations are found in 95% of Waldenstrom Macroglobulinaemia (WM) patients, aiding in distinguishing WM from other similar B-cell cancers, but 30% of suspected cases may have different diagnoses.
  • The 10-year survival rate is 73% for those with MYD88 mutations versus 90% for those without, with MYD88 status being a key factor in overall survival.
  • A significant number of WM patients with MYD88 mutations also develop Diffuse Large B-cell Lymphoma (DLBCL), leading to worse survival outcomes compared to those without the mutation.
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We propose a novel self-homodyne optical-electrical-optical clock recovery technique for binary phase-shift keying (BPSK) signals using commercial optical and electrical components. We present the principle of operation as well as a proof-of-concept experiment for a 10.7 Gb/s BPSK signal clock recovery transmitted over a dispersion-compensated link of 20 km of single-mode fiber.

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Ostensibly hydrophilic alginates are known to foul hydrophobic membranes, under various conditions. Here, controlled experiments have been conducted at high and low pH on the fouling of a polypropylene membrane by alginate and the results suggest that the observed fouling is due to an intrinsic property of the alginate. Thus quantum chemical calculations on the M and G monomers of alginate reveal that M adopts an equilibrium geometry that is hydrophilic on one face and hydrophobic on the other, i.

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The incidence and prognostic impact of nephropathy related to Waldenström macroglobulinaemia (WM) is currently unknown. We performed a retrospective study to assess biopsy-confirmed WM-related nephropathy in a cohort of 1391 WM patients seen at a single academic institution. A total of 44 cases were identified, the estimated cumulative incidence was 5·1% at 15 years.

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Whole-genome sequencing has identified highly prevalent somatic mutations including MYD88, CXCR4, and ARID1A in Waldenström macroglobulinemia (WM). The impact of these and other somatic mutations on transcriptional regulation in WM remains to be clarified. We performed next-generation transcriptional profiling in 57 WM patients and compared findings to healthy donor B cells.

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U.S. Army Forward Surgical Teams (FSTs) are elite, multidisciplinary units that are highly mobile, and rapidly deployable.

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We report a unidirectional frequency dissemination scheme for high-fidelity optical carriers deployable over telecommunication networks. For the first time, a 10 Gb/s Binary Phase Shift Keying (BPSK) signal from an ultra-narrow linewidth laser was transmitted through a field-installed optical fibre with round-trip length of 124 km between Cork City and town of Clonakilty, without inline optical amplification. At the receiver, using coherent communication techniques and optical injection-locking the carrier was recovered with noise suppression.

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We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography.

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We simulate and experimentally demonstrate a novel all-optical clock recovery technique for a BPSK OFDM superchannel. Four-wave mixing in SOAs is used to strip the modulation from the superchannel sub-carriers, two of which are filtered and beat together in a photodiode to recover the clock.

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Article Synopsis
  • - The study investigates the genetic foundation of Waldenström macroglobulinemia (WM) by conducting whole genome sequencing on 30 patients, including detailed analysis of 10 cases for both germline and tumor DNA.
  • - Key somatic mutations identified in WM patients include MYD88 (90% prevalence), CXCR4 (27%), and ARID1A (17%), with mutations linked to significant clinical syndromes found in CXCR4.
  • - The research also highlights prevalent gene losses and structural variants, particularly in chromosome 6, with genes such as PRDM2 and BTG1 being frequently deleted, offering insights into the mechanisms driving WM.
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We describe the first experimental demonstration of a novel all-optical phase discrimination technique, which can separate the two orthogonal phase components of a signal onto different frequencies. This method exploits nonlinear mixing in a semiconductor optical amplifier (SOA) to separate a 10.65 Gbaud QPSK signal into two 10.

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Myeloid differentiation factor 88 (MYD88) L265P somatic mutation is highly prevalent in Waldenström macroglobulinemia (WM) and supports malignant growth through nuclear factor κB (NF-κB). The signaling cascade(s) by which MYD88 L265P promotes NF-κB activation in WM remain unclear. By lentiviral knockdown or use of a MYD88 inhibitor, decreased phosphorylation of the NF-κB gatekeeper IκBα and survival occurred in MYD88 L265P-expressing WM cells.

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Two mechanisms that can make frequency conversion based on nonlinear mixing dependent on the phase of the input signal are identified. A novel phase-to-polarization converter that converts the orthogonal phase components of an input signal to two orthogonally polarized outputs is proposed. The operation of this scheme and a previously reported scheme at an increased symbol rate are simulated with semiconductor optical amplifiers (SOAs) as the nonlinear devices.

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  • Anemia is common in patients with Waldenström macroglobulinemia (WM) and isn’t always linked to bone marrow issues; hepcidin plays a role in iron absorption and can be elevated in these patients.
  • A study on 108 untreated anemic WM patients found that over half had low transferrin saturation (TSAT) levels, with some showing significantly low levels.
  • Patients with the lowest TSAT who received parenteral iron therapy demonstrated significant improvements in hematocrit, mean corpuscular volume, and TSAT, indicating that regular screening could help identify those needing this treatment.
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By whole-genome and/or Sanger sequencing, we recently identified a somatic mutation (MYD88 L265P) that stimulates nuclear factor κB activity and is present in >90% of Waldenström macroglobulinemia (WM) patients. MYD88 L265P was absent in 90% of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) patients. We therefore developed conventional and real-time allele-specific polymerase chain reaction (AS-PCR) assays for more sensitive detection and quantification of MYD88 L265P.

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  • Familial disease significantly impacts treatment outcomes in Waldenström macroglobulinemia (WM), with patients having familial disease showing worse results compared to those with sporadic disease.
  • However, patients with familial WM who are treated with bortezomib-containing regimens experience better treatment outcomes than those on non-bortezomib regimens.
  • The study emphasizes the need for further research to confirm these findings and suggests that the presence of familial disease should be considered when determining treatment approaches for WM.
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  • Waldenström's macroglobulinemia is an incurable form of lymphoma characterized by IgM secretion, and researchers aimed to identify its underlying genetic mutations through extensive genome sequencing.
  • Whole-genome sequencing identified a key mutation in the MYD88 gene (L265P variant) as being prevalent in a large majority of patients, suggesting it plays a significant role in the disease's pathogenesis.
  • Additional somatic mutations in genes like ARID1A were discovered in some patients, indicating potentially increased disease severity, while MYD88 mutations were absent in healthy individuals and other similar B-cell disorders.
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Background: Central venous catheters (CVCs) increase the risk of venous thromboembolism. We have previously demonstrated that pulmonary artery catheters are associated with a hypercoagulable state in an animal model and in patients. The purpose of this study is to determine whether the insertion of a CVC is associated with a similar response.

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We observe a near-ideal high speed amplitude impulse response in an SOA-EAM-SOA configuration under optimum conditions. Full amplitude recovery times as low as 10 ps with modulation depths of 70% were observed in pump-probe measurements. System behavior could be controlled by the choice of signal wavelength, SOA current biases and EAM reverse bias voltages.

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We report on the novel all-optical generation of duobinary (DB) and alternate-mark-inversion (AMI) modulation formats at 42.6 Gb/s from an input on-off keyed signal. The modulation converter consists of two semiconductor optical amplifier (SOA)-based Mach-Zehnder interferometer gates.

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We describe a novel SOA-based all-optical pure-phase modulator, and show how deleterious cross-gain modulation from the SOAs can be suppressed by utilizing an integrated interferometer structure. We experimentally demonstrate the use of the optical gate as a π/4 phase modulator producing 21.3 Gbaud 8PSK from 21.

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  • - The study investigates the relationship between family history of certain non-hematologic cancers (breast, colorectal, lung, ovarian, and prostate) and Waldenstrom macroglobulinemia (WM), which has been underexplored.
  • - Researchers analyzed medical records of patients with WM from 1999 to 2010 to evaluate if having first-degree relatives with these cancers influenced the likelihood of developing WM.
  • - Results indicate that a family history of prostate cancer is significantly associated with WM, showing the highest rate ratio, followed closely by breast cancer among sporadic cases, suggesting further research on these links could be beneficial.
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Simultaneous conversion of the two orthogonal phase components of an optical input to different output frequencies has been demonstrated by simulation and experiment. A single stage of four-wave mixing between the input signal and four pumps derived from a frequency comb was employed. The nonlinear device was a semiconductor optical amplifier, which provided overall signal gain and sufficient contrast for phase sensitive signal processing.

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