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1
Ntim, Stephen K. "Working Memory Failures and Comprehension Monitoring Impairments in Primary Readers." Psychology and Cognitive Sciences – Open Journal 9, no. 1 (December 27, 2023): 17–26. http://dx.doi.org/10.17140/pcsoj-9-170.
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Background This paper investigates the relationship between working memory (WM) failures and comprehension impairments in text comprehension among L2 primary readers in primary four through primary six in selected schools in Ghana. Method Five measures—decoding, vocabulary, working memory, comprehension monitoring, and reading comprehension—were used to test three research questions on the L2 primary reader’s ability to notice inconsistencies in paragraphs, stronger academic language, re-reading times for mismatched words in sentences, and self-reporting and comprehension. Results Major findings were that the primary readers’ ability to notice inconsistencies between paragraphs showed a significant average change between primary 4 and 5 in non-linear terms, with a correlation of r=-0.51 and a significant inverse correlation between the inability to see inconsistencies and the ability to recognize them. Vocabulary had a stronger positive relationship with comprehension monitoring (β=0.07, p<0.001) for primary five and six and primary four and five (β=0.04, p<0.001), respectively. Conclusion Decoding, vocabulary, and WM were found to be predominant factors for reading (β=0.46, p<0.00010), (β=0.37, p<0.0001), and (β=0.45, p<0.0001), while vocabulary and WM combination accounted for 25% of the additional reading variance in primary six, suggesting the significance of WM on self-reporting as a comprehension measure. The recommended classroom practice was for teachers to be mindful of working memory capacities, imposing mental demands on struggling L2 pupils.
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Pavlakis, K. G., N. Hatzianastassiou, C. Matsoukas, A. Fotiadi, and I. Vardavas. "ENSO surface shortwave radiation forcing over the tropical Pacific." Atmospheric Chemistry and Physics Discussions 8, no. 2 (April 7, 2008): 6697–728. http://dx.doi.org/10.5194/acpd-8-6697-2008.
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Abstract. We have studied the spatial and temporal variation of the downward shortwave radiation (DSR) at the surface of the Earth during ENSO events for a 21-year period over the tropical and subtropical Pacific Ocean (40° S–40° N, 90° E–75° W). The fluxes were computed using a deterministic model for atmospheric radiation transfer, along with satellite data from the ISCCP-D2 database, reanalysis data from NCEP/NCAR for the key atmospheric and surface input parameters, and aerosol parameters from GADS (acronyms explained in main text). A clear anti-correlation was found between the downward shortwave radiation anomaly (DSR-A) time-series, in the region 7° S–5° N 160° E-160° W located west of the Niño-3.4 region, and the Niño-3.4 index time-series. In this region where the highest in absolute value DSR anomalies are observed, the mean DSR anomaly values range from −45 Wm−2 during El Niño episodes to +40 Wm−2 during La Niña events. Within the Niño-3.4 region no significant DSR anomalies are observed during the cold ENSO phase in contrast to the warm ENSO phase. A high correlation was also found over the western Pacific (10° S–5° N, 120–140° E), where the mean DSR anomaly values range from +20 Wm−2 to −20 Wm−2 during El Niño and La Niña episodes, respectively. There is also convincing evidence that the time series of the mean downward shortwave radiation anomaly in the north subtropical Pacific region 7–15° N 150–170° E, precedes the Niño-3.4 index time-series by about 7 months. Thus, the downward shortwave radiation anomaly is a complementary index to the SST anomaly for the study of ENSO events and can be used to assess whether or not El Niño or La Niña conditions prevail.
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Ikeda, Yoshifumi, Yosuke Kita, Yuhei Oi, Hideyuki Okuzumi, Silvia Lanfranchi, Francesca Pulina, Irene Cristina Mammarella, Katie Allen, and David Giofrè. "The Structure of Working Memory and Its Relationship with Intelligence in Japanese Children." Journal of Intelligence 11, no. 8 (August 18, 2023): 167. http://dx.doi.org/10.3390/jintelligence11080167.
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There is a host of research on the structure of working memory (WM) and its relationship with intelligence in adults, but only a few studies have involved children. In this paper, several different WM models were tested on 170 Japanese school children (from 7 years and 5 months to 11 years and 6 months). Results showed that a model distinguishing between modalities (i.e., verbal and spatial WM) fitted the data well and was therefore selected. Notably, a bi-factor model distinguishing between modalities, but also including a common WM factor, presented with a very good fit, but was less parsimonious. Subsequently, we tested the predictive power of the verbal and spatial WM factors on fluid and crystallized intelligence. Results indicated that the shared contribution of WM explained the largest portion of variance of fluid intelligence, with verbal and spatial WM independently explaining a residual portion of the variance. Concerning crystallized intelligence, however, verbal WM explained the largest portion of the variance, with the joint contribution of verbal and spatial WM explaining the residual part. The distinction between verbal and spatial WM could be important in clinical settings (e.g., children with atypical development might struggle selectively on some WM components) and in school settings (e.g., verbal and spatial WM might be differently implicated in mathematical achievement).
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Pavlakis, K. G., N. Hatzianastassiou, C. Matsoukas, A. Fotiadi, and I. Vardavas. "ENSO surface shortwave radiation forcing over the tropical Pacific." Atmospheric Chemistry and Physics 8, no. 18 (September 18, 2008): 5565–77. http://dx.doi.org/10.5194/acp-8-5565-2008.
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Abstract. We have studied the spatial and temporal variation of the downward shortwave radiation (DSR) at the surface of the Earth during ENSO events for a 21-year period over the tropical and subtropical Pacific Ocean (40° S–40° N, 90° E–75° W). The fluxes were computed using a deterministic model for atmospheric radiation transfer, along with satellite data from the ISCCP-D2 database, reanalysis data from NCEP/NCAR for the key atmospheric and surface input parameters, and aerosol parameters from GADS (acronyms explained in main text). A clear anti-correlation was found between the downward shortwave radiation anomaly (DSR-A) time-series, in the region 7° S–5° N 160° E–160° W located west of the Niño-3.4 region, and the Niño-3.4 index time-series. In this region where the highest in absolute value DSR anomalies are observed, the mean DSR anomaly values range from −45 Wm−2 during El Niño episodes to +40 Wm−2 during La Niña events. Within the Niño-3.4 region no significant DSR anomalies are observed during the cold ENSO phase in contrast to the warm ENSO phase. A high correlation was also found over the western Pacific (10° S–5° N, 120–140° E), where the mean DSR anomaly values range from +20 Wm−2 to −20 Wm−2 during El Niño and La Niña episodes, respectively. There is also convincing evidence that the time series of the mean downward shortwave radiation anomaly in the off-equatorial western Pacific region 7–15° N 150–170° E, precedes the Niño-3.4 index time-series by about 7 months and the pattern of this anomaly is indicative of ENSO operating through the mechanism of the western Pacific oscillator. Thus, the downward shortwave radiation anomaly is a complementary index to the SST anomaly for the study of ENSO events and can be used to assess whether or not El Niño or La Niña conditions prevail.
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Chalmers, Kerry A., and Emily E. Freeman. "Working Memory Power Test for Children." Journal of Psychoeducational Assessment 37, no. 1 (September 15, 2017): 105–11. http://dx.doi.org/10.1177/0734282917731458.
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Low working memory (WM) capacity has been linked to poor academic performance and problem behavior. Availability of easy-to-administer screening tests would facilitate early detection of WM deficits. This study investigated the psychometric properties of the Working Memory Power Test for Children (WMPT) in 170 Australian schoolchildren (8½-11 years). Reliability (internal consistency) and validity of WMPT accuracy scores were examined. WMPT accuracy predicted achievement in reading, numeracy, and spelling. The results provide preliminary evidence of reliability and validity that supports interpretation of the WMPT accuracy score. With additional research, the WMPT could be valuable as an easy-to-administer screener for WM deficits.
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Regmi, Santosh, and Sunil Adhikary. "Solar Energy Potential in Kathmandu Valley, Nepal." Journal of Hydrology and Meteorology 8, no. 1 (August 30, 2016): 77–82. http://dx.doi.org/10.3126/jhm.v8i1.15576.
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Meteorological data such as solar radiation (1975-1984, and 2002-2010) and sunshine duration (1968-2004) were analyzed to study temporal characteristics of solar energy and investigate solar energy potential in Kathmandu valley. Pre-monsoon and post monsoon seasons have higher mean monthly sunshine duration (about 8 hours/day) than summer (about 5 hours/day) and winter (about 7 hours/day) seasons over Kathmandu. Pre-monsoon and monsoon seasons receive solar energy of about 190 Wm-2 and 170 Wm-2 respectively. The winter season receives the least amount of solar radiation (135 Wm-2). Approximately 220 MW of solar electricity can be produced in Kathmandu that will substantially fulfill current energy demand and reduce environmental pollution in the valley by replacing fossil fuels with clean solar electricity.Journal of Hydrology and Meteorology, Vol. 8(1) 2012, p.77-82
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Ciccarelli, Bryan, Christopher J. Patterson, Zachary Hunter, Christina Hanzis, Thea Ioakimidis, Robert Manning, Guang Yang, et al. "Patients with Waldenstrom's Macroglobulinemia Are Often Hypoferremic That Is Refractory to Oral Iron Repletion and Responsive to Parental Iron Infusions, and Demonstrate Elevated Levels of Hepcidin." Blood 114, no. 22 (November 20, 2009): 2952. http://dx.doi.org/10.1182/blood.v114.22.2952.2952.
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Abstract Abstract 2952 Poster Board II-928 Background: Patients with Waldenstrom's macroglobulinemia (WM) often present with anemia, that can occur independent of bone marrow disease involvement, serum IgM levels, and in the absence of any hemolysis (Treon, Blood 2009). Iron deficiency is commonly observed in WM patients, and is often oral iron refractory. Parenteral administration of iron (Ferrlicit) in such patients can lead to improvements in hematocrit in patients who are oral iron refractory as shown below in Table 1: As such, we investigated mechanisms by which oral iron uptake could be impaired in patients with WM. Hepcidin is a peptide which acts as a master regulator of iron homeostasis by binding to and disabling the only known iron-export protein, ferroportin, resulting in the inhibition of iron transfer from enterocytes and macrophages into the circulation. We therefore sought to delineate the role of Hepcidin in WM patients presenting with and without anemia, and in those patients who did not respond to oral iron intake. Patients and Methods: Serum levels of Hepcidin were determined in 53 previously untreated patients with WM [Median Age: 63; BM Involvement 40%; Beta 2 Microglobulin (B2M) 2.6 g/L; Hematocrit 34.2%; Iron 67 ug/dL; TIBC 321 ug/dL] along with 20 healthy donors [Median Age: 63.5, Female N=8, Male N=12] using the Hepcidin-P competitive ELISA for hepcidin-25, the biologically-active form of the hormone [Intrinsic LifeSciences, La Jolla, CA USA]. Of the patients examined, 45 were anemic, 12 were hypoferremic [<37-170 mg/dL]. All but 5 individuals had normal TIBC levels [210-480 mg/dL]. Results: Serum Hepcidin levels were elevated among all WM patients [107.5 ng/mL, range 11.3-689 ng/mL] versus healthy donors [91.8 ng/mL, range 12.2-211.6 ng/mL; p=.04]. Levels of Hepcidin positively correlated with BM disease involvement (p=0.004; Spearmans rho=0.4), and inversely with hematocrit (p=0.08; Spearman's rho=-.24) [Figure 1,2]. Among the 45 WM patients who demonstrated anemia, the median level of Hepcidin was higher at 118.5 ng/mL [Range 11.3-689 ng/mL; p=0.025 versus healthy donors]. Among 5 WM patients who failed to respond to oral iron repletion and who subsequently responded to parenteral iron (Table 1), the median Hepcidin level was 189.1 (range 40.6-444.1 ng/mL). Among non-anemic WM patients, hepcidin levels were lower [66.5 ng/mL; range 31.7-401.8 ng/mL; p=0.35 versus anemic WM patients), though these patients demonstrated a lower bone marrow disease burden (30% vs. 50%; p=0.03). Conclusions: Hepcidin levels are elevated in patients with WM, and show a positive correlation with bone marrow disease burden, and an inverse relationship with hematocrit. Importantly, higher levels of Hepcidin may be associated with refractoriness to oral iron intake. Further studies addressing the role of Hepcidin in the management of WM related anemia are warranted. Disclosures: No relevant conflicts of interest to declare.
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Landgren, Ola, Sigurdur Y. Kristinsson, Lynn R. Goldin, Neil E. Caporaso, Cecilie Blimark, Ulf-Henrik Mellqvist, Anders Wahlin, Magnus Bjorkholm, and Ingemar Turesson. "Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden." Blood 114, no. 4 (July 23, 2009): 791–95. http://dx.doi.org/10.1182/blood-2008-12-191676.
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Abstract Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
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Jiang, Yunlu, Ying Kan, and Huaining Chen. "Heterogeneous Microstructure-Induced Creep Failure Responses in Various Sub-Zones of Modified 310S Welded Joints." Metals 12, no. 1 (January 7, 2022): 116. http://dx.doi.org/10.3390/met12010116.
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In order to reveal the creep failure behavior of novel modified 310S austenite steel welded joints, the creep life and microstructure evolution of the 310S austenite steel welded joints were investigated in this study. The rupture life was assessed to estimate the damage of the welded joint based on creep rupture tests performed at 600 °C in the stress range of 170–238 MPa. Compared with WM, HAZ facilitated the occurrence of creep failure in long term creep due to the combination of a smaller hardness value, a more heterogenous microstructure accompanied by coarsened M23C6, a larger grain size, higher KAM and Schmid factor. Discontinuous Laves phases appeared near the boundaries between the δ-ferrite and γ-austenite grains in the WM, and dislocation strengthening and precipitation strengthening were observed near the boundary in the BM. Furthermore, segregation elements were detected by APT and EDS adjacent to the boundary. Cr and C segregation near grain boundaries weaken the creep resistance in long term creep service.
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Berlanga, Oscar, Jane Birtwistle, Syreeta Allen, Gemma Malin, Cristina Simion, Habib El-Khoury, Julia Colchie, et al. "Multi-Center Clinical Validation of a Mass Spectrometry Immunoassay for the Diagnosis and Monitoring of Multiple Myeloma and Associated Disorders." Blood 142, Supplement 1 (November 28, 2023): 3667. http://dx.doi.org/10.1182/blood-2023-189050.
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Introduction: Mass spectrometry (MS) technology holds great promise for the investigation of monoclonal proteins (M proteins) in peripheral blood. We present results from a multi-center clinical validation study using quantitative immunoprecipitation MS (QIP-MS). QIP-MS combines isotype-specific immunopurification with matrix-assisted laser-desorption ionization MS, and offers automated, sensitive detection, isotyping and quantification of M proteins. It reports the mass/charge ratio (m/z) of the involved light chain, which serves as molecular fingerprint for monitoring the M protein. Methods: The study included 460 diagnosed monoclonal gammopathy (MG) patients (160 multiple myeloma (MM), 112 smoldering MM (SMM), 120 monoclonal gammopathy of undetermined significance (MGUS), 47 Waldenström's Macroglobulinemia (WM), and 21 AL amyloidosis), and 170 disease controls for assessing diagnostic sensitivity and specificity. Sixty-four MM patients with 439 follow-up samples and 10 WM patients with 91 follow-up samples were included to evaluate the ability of QIP-MS to detect M protein changes related to treatment. Median follow up was 19 and 15 months, respectively. Serum samples were retrospectively analyzed at three sites. QIP-MS was carried out using the automated EXENT® solution (in development, The Binding Site, part of Thermo Fisher Scientific). The assay's diagnostic sensitivity and specificity were calculated based on categorizing results as positive or negative. A positive result was defined in baseline samples as the presence of an M protein which was either an intact immunoglobulin ≥0.200 g/L or a light chain only. Results by QIP-MS were also compared to serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). QIP-MS response categories were defined based on M protein changes per international guidelines criteria, and compared to response categories assigned by the treating physician. Complete response (CR) was defined as absence of the M-peak that was observed at baseline, using isotype and m/z value of ±4 as criterion for identity. Results: The overall diagnostic sensitivity of QIP-MS in this study was 95.0%: 93.3% for MGUS; 100.0% for SMM; 94.4% for MM; 100.0% for WM; and 71.4% for AL amyloidosis. The diagnostic specificity of the assay was 68.2%. QIP-MS identified an M protein in more MG patients compared to SPE: 437 (95.0%) vs 398 (86.5%). The positivity rate by QIP-MS vs SPE was 93.3% vs 84.2% in MGUS; 100% vs 92.9% in SMM; 94.3% vs 85.0% in MM; 100% vs 100% in WM and 71.4% vs 47.6% in AL amyloidosis. Method comparison demonstrated a Passing-Bablok slope of 0.8 to 1.2 between QIP-MS and SPE for the quantification of M proteins for each disease group and for each isotype, except for monoclonal IgM and in WM (slope of 1.58). In SPE-positive MG patients, the overall concordance between QIP-MS and IFE for M protein isotype was 97%. The overall concordance rate between QIP-MS response categories and standard response assignment was 55% for MM and 56% for WM: 48% for progressive disease (PD); 63% for stable disease (SD); 46% for minimal response (MR); 71% for partial response (PR); 66% for very good partial response (VGPR); and 25% for CR in MM patients. Among 73 responses categorized as CR, QIP-MS produced a positive result for the original clone in 55 (75.3%) cases. Concordance rates in WM patients were 71% for PD%; 30% for SD; 38% for MR; and 74% for PR; no VGPR or CR were reported by either method. Conclusions: In this study, QIP-MS demonstrated the potential for same or superior diagnostic sensitivity compared to SPE, high concordance with IFE for the M protein isotype and good quantitative agreement with SPE measurements of the M proteins. It reported higher IgM values compared to SPE, likely due to reliance on turbidimetric immunoglobulin measurement for quantitations. Diagnostic specificity was impacted by the identification of minor M proteins, not detectable by SPE, and whose clinical significance requires further investigation. QIP-MS demonstrated “moderate” to “fair” agreement for response assignment in MM and WM, respectively, mostly due to the detection of residual M proteins in a significant proportion of patients in CR, in line with its enhanced analytical sensitivity. These data support the use of QIP-MS as an aid in the diagnosis and monitoring of MGs.
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Hensel, Manfred, Jürgen Brust, Christoph Plöger, Dieter Schuster, Marie-Luise Memmer, Michael Rieger, Lara Hensel, et al. "Excellent Long-Term Survival of Patients with Waldenström‘s Macroglobulinemia (WM) treated in Private Oncology Practices and a University hospital with different Treatment Strategies." Blood 118, no. 21 (November 18, 2011): 2671. http://dx.doi.org/10.1182/blood.v118.21.2671.2671.
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Abstract Abstract 2671 Background: WM is a rare type of malignant B-cell lymphoma, defined as a lymphoplasmocytic lymphoma in bone marrow and a monoclonal gammopathy of immunoglobulin-M (IgM) type. Due to the paucity of large clinical trials, a standard treatment regimen is still controversial. The purpose of this study was to compare the standard treatment and outcome of patients (pts) treated in private oncology practices (PP) and a university hospital (UH) in a region of southern Germany (Nordbaden). Methods: We retrospectively reviewed the charts of all pts with WM of the last 2 decades of 4 PP in Mannheim, Heidelberg, Karlsruhe and Speyer and the department of hematology of the University of Heidelberg. Results: 170 patients with WM could be identified, 74 from PP, 96 from the UH. The median age of the 170 pts was 63.3 years (range 29.1–88.5). The clinical symptoms were splenomegaly in 21.2%, hyperviscosity in 15.9%, lymphadenopathy in 15.9%, and polyneuropathy in 11.2%. 12.9% had a previous phase of IgM-MGUS. Pts from PP were older (median 65.3 vs. 62.5, p=0.01). Mean hemoglobine level at diagnosis was lower in pts from UH (11.4 vs. 12.2, p=0.04). There was no significant difference in mean platelet count, IgM and ß2-microglobuline level at diagnosis. 54% of pts from PP have received treatment during the observation time, as compared to 78.1% of the UH (p<0.001). The most common first line treatment protocols of PP were Chlorambucil (17/40, 42.5%), Bendamustin (17.5%) and Rituximab(R)-Bendamustin (17.5%). The UH most commonly administered R-Pentostatin-Cyclophosphamide (28%), Chlorambucil (17.3%) and COP (16%). 35% of the treated pts of PP have received R, as compared to 62.6% of the pts of the UH (p<0.001). 60% of the treated pts of PP have received Bendamustin, as compared to 8% of the pts of the UH (p<0.001). The time to first treatment was significantly shorter in pts from the UH (median 13.7 mo.) as compared to PP (52.9 mo.) (p=0.05). Median overall survival of all pts was 25.0 yrs and did not differ between PP and UH. Conclusion: Pts with WM treated in PP were older and had higher initial hemoglobin levels as compared to pts from the UH. Treatment differs significantly between PP and UH. Time to first treatment was significantly shorter in pts from UH. Overall survival was excellent, and better than reported previously. Disclosures: Hensel: Roche: Honoraria, Research Funding; Mundipharma: Research Funding.
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Doyle, A. E., J. Wozniak, T. E. Wilens, A. Henin, L. J. Seidman, C. Petty, R. Fried, L. M. Gross, S. V. Faraone, and J. Biederman. "Neurocognitive impairment in unaffected siblings of youth with bipolar disorder." Psychological Medicine 39, no. 8 (December 11, 2008): 1253–63. http://dx.doi.org/10.1017/s0033291708004832.
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BackgroundThere is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and ‘executive’ functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis.MethodSubjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey–Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test – Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD).ResultsPrincipal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged ⩾12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor.ConclusionsNeurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.
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Ohm, Daniel T., Katheryn A. Q. Cousins, Sharon X. Xie, Claire Peterson, Corey T. McMillan, Lauren Massimo, Katya Raskovsky, et al. "Signature laminar distributions of pathology in frontotemporal lobar degeneration." Acta Neuropathologica 143, no. 3 (January 8, 2022): 363–82. http://dx.doi.org/10.1007/s00401-021-02402-3.
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AbstractFrontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.
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Rammelaere, Reint‐Jan. "EVANGELISM: LEARNING FROM THE PAST. By MichaelGreen. Grand Rapids, MI: Wm. B. Eerdmans Publishing Co, 2023. Pp. xiv + 170. Paperback, $22.99." Religious Studies Review 50, no. 1 (March 2024): 151–52. http://dx.doi.org/10.1111/rsr.16995.
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Rahim, Muhammad Abdul, Muhammad Imran, Muhammad Kamran Khan, Muhammad Haseeb Ahmad, Muhammad Nadeem, Waseem Khalid, Jose Manuel Lorenzo, Mohamed M. Afifi, Ammar Al-Farga, and Moneera O. Aljobair. "Omega-3 Fatty Acid Retention and Oxidative Stability of Spray-Dried Chia–Fish-Oil-Prepared Microcapsules." Processes 10, no. 11 (October 25, 2022): 2184. http://dx.doi.org/10.3390/pr10112184.
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Background: Omega-3 fatty acids are essential fatty acids that the body cannot create itself; thus, they must be obtained from functional foods. Therefore, the food processing industries are becoming more interested in the production of omega-3 enriched food products, as consumers and healthcare organizations are increasingly demanding functional foods with minimal fatty acid loss and higher oxidative stability. Moreover, the stability of long-chain, polyunsaturated fatty acids in functional foods is a major challenge for the food processing industries. Therefore, the spray drying method was used to prepare spray-dried microcapsules (SDMs) with the minimum loss of, and more stable, fatty acids. Methods: In this study, emulsion blends of chia seed oil (CSO, 50%) and fish oil (FO, 50%) were spray-dried using varied operating conditions, including the inlet air temperature (IAT) (125, 140, 155, 170, and 185 °C), wall material (WM) (5, 10, 15, 20, and 25%), pump speed (PS) (3, 4, 5, 6, and 7 mL/min), and needle speed (NS) (3, 5, 7, 9, and 11 S). Results: The maximum loss of ALA in the spray-dried microcapsules (SDMs) was observed (9.90 ± 0.40%) at 170 °C, and the minimum loss was 4.18 ± 0.20% in run order 9. A similar trend was observed in the maximum retention loss of EPA and DHA (9.71 ± 0.39% and 9.77 ± 0.39%) at a high temperature of 170 °C, while the minimum losses of EPA and DHA were observed in run order 9. Furthermore, the maximum peroxide value (PV) of the SDMs was observed at a lower temperature of 140 °C (1.45 ± 0.19 meq O2/kg), and the minimum PV was 1.33 ± 0.16 meq O2/kg. Conclusions: Overall, based on the results, we concluded that the oxidative stability of the SDMs was improved and that it can be used as a fortifying agent in the processing of many food products.
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Goss, Kevin Colin William, Chris Gale, Rachel Malone, Nicholas Longford, Kirsty Ratcliffe, and Neena Modi. "Effect of surfactant dose on outcomes in preterm infants with respiratory distress syndrome: the OPTI-SURF study protocol." BMJ Open 10, no. 12 (December 2020): e038959. http://dx.doi.org/10.1136/bmjopen-2020-038959.
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IntroductionRespiratory distress syndrome is a condition seen in preterm infants primarily due to surfactant insufficiency. European guidelines recommend the dose and method of surfactant administration. However, in routine practice, clinicians often use a ‘whole vial’ approach to surfactant dosing. The aim of this study is to assess whether in preterm infants of gestational age 36+6weeks+daysor less, a low first dose of surfactant (100–130 mg/kg) compared with a high first dose (170–200 mg/kg) affects survival with no mechanical ventilation on either on postnatal days 3 and 4, and other outcomes.Methods and analysisIn this prospective, observational study, we will use the National Neonatal Research Database as the main data source. We will obtain additional information describing the dose and method of surfactant administration through the neonatal EPR system. We will use propensity scores to form matched groups with low first dose and high first dose for comparison.Ethics and disseminationThis study was approved by the West Midlands—Black Country Research Ethics Committee (REC reference: 18/WM/0132; IRAS project ID: 237111). The results of the research will be made publicly available through presentations at local, national or international conferences and will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03808402.
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Buttar, Noman Ali, Hu Yongguang, Josef Tanny, M. Waqar Akram, and Abdul Shabbir. "Fetch Effect on Flux-Variance Estimations of Sensible and Latent Heat Fluxes of Camellia Sinensis." Atmosphere 10, no. 6 (June 1, 2019): 299. http://dx.doi.org/10.3390/atmos10060299.
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Precise estimation of surface-atmosphere exchange is a major challenge in micrometeorology. Previous literature presented the eddy covariance (EC) as the most reliable method for the measurements of such fluxes. Nevertheless, the EC technique is quite expensive and complex, hence other simpler methods are sought. One of these methods is Flux-Variance (FV). The FV method estimates sensible heat flux (H) using high frequency (~10Hz) air temperature measurements by a fine wire thermocouple. Additional measurements of net radiation (Rn) and soil heat flux (G) allow the derivation of latent heat flux (LE) as the residual of the energy balance equation. In this study, the Flux Variance method was investigated, and the results were compared against eddy covariance measurements. The specific goal of the present study was to assess the performance of the FV method for the estimation of surface fluxes along a variable fetch. Experiment was carried out in a tea garden; an EC system measured latent and sensible heat fluxes and five fine-wire thermocouples were installed towards the wind dominant direction at different distances (fetch) of TC1 = 170 m, TC2 = 165 m, TC3 = 160 m, TC4 = 155 m and TC5 = 150 m from the field edge. Footprint analysis was employed to examine the effect of temperature measurement position on the ratio between 90% footprint and measurement height. Results showed a good agreement between FV and EC measurements of sensible heat flux, with all regression coefficients (R2) larger than 0.6; the sensor at 170 m (TC1), nearest to the EC system, had highest R2 = 0.86 and lowest root mean square error (RMSE = 25 Wm−2). The estimation of LE at TC1 was also in best agreement with eddy covariance, with the highest R2 = 0.90. The FV similarity constant varied along the fetch within the range 2.2–2.4.
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Ayyaz, Muhammad, Zulqurnain Khan, Nabila Tabassam, Tariq Sultan, Amjad Saeed, and Muhammad Shan. "Isolation and Characterization of Plant Growth Promoting Rhizobacteria for Growth Promotion of Rice (Oryza sativa L.) and Wheat (Triticum aestivum)." Pakistan Journal of Biochemistry and Biotechnology 2, no. 2 (December 31, 2021): 177–94. http://dx.doi.org/10.52700/pjbb.v2i2.66.
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The use of rhizobacteria for plant growth enhancement is decades old. Still, in this era of the 21st century, biofertilizers have become the need of the day due to the health and environmental concerns associated with chemical fertilizers and pesticides. Rhizobacteria strains were isolated from the rhizosphere of rice and wheat. The selected bacterial strains' nitrogen fixation, indole acetic acid (IAA) production, phosphorus solubilization, and antifungal activity were determined on morphological, biochemical, and molecular levels. Production of IAA ranged from 6 µg/ml to 29.33 µg/ml. Ethylene production (C2H4/hr) varied from 2 µmoles to 9.8 µmoles. Maximum Phosphorus Solubilization index (7), decrease in pH (4) and Solubilization % age (0.49) was observed in WM-2 (wheat microbe). Promising results were obtained concerning antifungal activity against Rhizoctonia solani and Fusarium sp. The effect of the potential PGPR strains on the germination of rice and wheat was significantly positive in Petri plates. In the case of rice, the highest shoot length (29.27 cm) was observed by inoculation with RPR-33 (Rice isolate), and the most increased root length (9.33 cm) was observed in the treatment inoculated with RPR-42. The highest shoot fresh weight (476.67 mg/plant) was recorded in the treatment inoculated with RPR-42. The maximum root weight was 170 mg/plant in the same treatment. For wheat, all recorded growth parameters were improved significantly by wheat microbe WM-5. All the PGPR isolates showed positive results for growth parameters of wheat and rice on inoculation. So, it is suggested that these PGPR isolates may be used in potential biofertilizers.
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Shrestha, Arun Kumar, Arati Thapa, and Hima Gautam. "Solar Radiation, Air Temperature, Relative Humidity, and Dew Point Study: Damak, Jhapa, Nepal." International Journal of Photoenergy 2019 (December 11, 2019): 1–7. http://dx.doi.org/10.1155/2019/8369231.
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Monitoring and prediction of the climatic phenomenon are of keen interest in recent years because it has great influence in the lives of people and their environments. This paper is aimed at reporting the variation of daily and monthly solar radiation, air temperature, relative humidity (RH), and dew point over the year of 2013 based on the data obtained from the weather station situated in Damak, Nepal. The result shows that on a clear day, the variation of solar radiation and RH follows the Gaussian function in which the first one has an upward trend and the second one has a downward trend. However, the change in air temperature satisfies the sine function. The dew point temperature shows somewhat complex behavior. Monthly variation of solar radiation, air temperature, and dew point shows a similar pattern, lower at winter and higher in summer. Maximum solar radiation (331 Wm-2) was observed in May and minimum (170 Wm-2) in December. Air temperature and dew point had the highest value from June to September nearly at 29°C and 25°C, respectively. The lowest value of the relative humidity (55.4%) in April indicates the driest month of the year. Dew point was also calculated from the actual readings of air temperature and relative humidity using the online calculator, and the calculated value showed the exact linear relationship with the observed value. The diurnal and nocturnal temperature of each month showed that temperature difference was relatively lower (less than 10°C) at summer rather than in winter.
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Tohidi‐Esfahani, I., A. Warden, E. Malunis, P. DeNardis, J. Bomsztyk, S. D'Sa, M. J. Kersten, et al. "PF495 WHIMSICAL (WALDENSTRÖM'S MACROGLOBULINEMIA STUDY INVOLVING CART‐WHEEL): A GLOBAL PATIENT‐DERIVED DATA REGISTRY MAPPING TREATMENT AND QUALITY OF LIFE DATA." HemaSphere 3, S1 (June 2019): 200–201. http://dx.doi.org/10.1002/j.2572-9241.2019.tb00094.x.
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Background:Patient‐derived data can increase breadth of knowledge in rare cancers like Waldenström's Macroglobulinemia (WM), including Patient‐reported outcomes (PROs).Aims:This study utilised www.cart‐wheel.org, an ethically‐approved online rare cancer database for patient‐derived data, and harnessed the digital connectedness of WM patients globally, to develop a continuously expanding dataset and platform for hypothesis generation around WM.Methods:An ethics committee‐approved WM‐specific extension to the www.cart‐wheel.org questionnaire, developed by clinician and patient investigators, was released June 2016. Participants complete consent online and enter their symptom, pathology and treatment data. Recruitment strategies driven by the International Waldenström's Macroglobulinemia Foundation investigators utilised multiple social media platforms. Inclusion of the EORTC‐QLQ‐C30 quality of life (QoL) questionnaire went live in October 2018, with targeted recruitment messaging sent out in February 2019.Results:355 patients from 17 countries have been recruited, predominantly from USA (48%) and Australia (22%), with male predominance (62%). Median age at diagnosis was 61 (range 24–83), median IgM 27.4 g/L (IQR 13.1–40.3 g/L, n = 130) and median hemoglobin 112 g/L (IQR 97–128 g/L, n = 134). Of the 279 (79%) patients providing symptoms at diagnosis, fatigue/muscle weakness was most common (45%) and 32% were asymptomatic. Using the Impact of Event Scale for symptoms of post‐traumatic stress disorder (PTSD) resulting from a cancer diagnosis, at median 50 months post‐diagnosis, the mean score among 305 patients was 5.8 (no stress = 0, maximal stress = 24), with 29/305 (10%) scoring ≥13 (PPV 94% for PTSD, Thoresen et al, 2010). 41 different first‐line therapeutic combinations were documented by 238 patients. Median time from diagnosis to first treatment for USA patients was 50 days (IQR 15–423, n = 104) vs Rest of World (ROW) 170 days (IQR 22–775, n = 120), (p = 0.06). Of the 213 therapies listed by 108 USA patients, 59 (28%) were reported as accessed by government or public program and 8 (4%) via clinical trial participation, whereas among ROW patients (n = 113), 122/225 (54%) were government/public program accessed and 31/225 (14%) through clinical trials (p = 0.0001 and p = 0.0002, respectively). In the three weeks following targeted messaging, 156 patients responded to the QoL questions. Early analysis of raw scores for overall health (Q29) and overall quality of life (Q30), ranging from 1: very poor to 7: excellent, demonstrated means of 5.1 and 5.8, respectively. Respondents who received BTK inhibitors (BTKi, n = 33) had comparable Q29 and Q30 scores compared to those who received non‐BTKi treatment (n = 84): Q29 means 5.8 vs 5.5, Q30 6.1 vs 5.7 (p = 0.2 and p = 0.13, respectively). This was despite median 2 (IQR 1–4) lines of treatment in the BTKi group compared to median 1 (IQR 1–2) in the non‐BTKi group.Summary/Conclusion:The WhiMSICAL study is a robust global patient‐derived data platform, providing insight into patient symptoms, including WM‐related stress responses, diversity of therapies and QoL. Further recruitment (Project 1000) and encouragement of more complete and continuous data entry will increase the utility of WhiMSICAL. As an expanding and increasingly reliable body of data, WhiMSICAL has the potential to map real‐world PROs, and provide a scientific and ethically‐approved portal for patients’ voices globally.
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Tomkins, Oliver, Joshua Bomsztyk, Helen McCarthy, Jaimal Kothari, Dima El-Sharkawi, Charalampia Kyriakou, Guy Pratt, Ali Rismani, and Shirley D'Sa. "An Analysis from the WM UK Rory Morrison Registry: Waldenström's Macroglobulinaemia Patient Demographics, Disease Characteristics and Evolving Treatment Choices." Blood 134, Supplement_1 (November 13, 2019): 4016. http://dx.doi.org/10.1182/blood-2019-129212.
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Background Waldenström's macroglobulinaemia (WM) is a rare non-Hodgkin B cell lymphoma. Given its rarity, information about both patient demographics and disease characteristics are limited. Treatment is indicated for symptomatic patients and treatment regimens have evolved significantly in recent years. The Rory Morrison Registry (RMR) has comprehensive patient data available for analysis. We seek to draw conclusions about UK patient demographics and disease characteristics, and evaluate how treatment practices have evolved. Methods The RMR was searched for all patients with a diagnosis of WM. Patient demographics, disease characteristic, pathology results, treatment information and survival status retrieved. Kaplan Meier and log rank analysis was performed. Results 671 patients were identified from 19 different UK centres. Median age at diagnosis was 64 years (range 27-92, figure 1). Year of diagnosis ranged from 1978 to 2019, with 7 patients diagnosed <1990, 31 1990-1999, 200 2000-2009, and 433 since 2010. Male to female ratio was 1.62:1. 90.4% were Caucasian, 5.9% Asian, 1.3% Afro-Caribbean, 0.7% mixed, and 1.6% of other ethnicity. Median haemoglobin at diagnosis was 112g/L (range 33-170), platelet count 242 (3-806), B2M 3 (range 0.2-56.3) and M-protein 17g/L (range 0-110.5). Median bone marrow infiltration was 40% (range 0-100%), with 35% lymphocytes and 5% plasma cell. MYD88 L265P mutations were detected in 160/190 patients (84.2%). CXCR4 mutations, for which testing is not widely available, were detected in 20/76 patients (26.3%). Peripheral neuropathy was seen in 74 patients, with 28 anti-MAG antibody positive. Other manifestations at diagnosis included cryoglobulinaemia (26), amyloidosis (12) and Schnitzler's syndrome (7). 2/317 patients were HIV positive, 4/341 HCV antibody positive, 27/334 HBSAb positive, and 12/327 HBCAb positive. IPSSWM score at diagnosis was available for 352 patients, with a low score in 122 (34.7%), intermediate score in 103 (29.3%), and high score in 123 (45%). 440 patients (65.6%) had received treatment, with a median time from diagnosis to treatment of two months (range 0-312). Indications for first line treatment initiation were: 35% paraprotein-related, 30% lymphoma-related , 2.1% B-symptoms, and a combination of indications for the remainder. Hyperviscosity was the treatment indication in 24.8% of patients, fatigue in 21.6% and peripheral neuropathy in 9.8%. At treatment commencement, 47% of patients had a haemoglobin of <100g/L. CNS involvement was a feature in 1.5% and 1.5% high grade transformation (HGT). Lines of therapy received was one in 43.6%, two in 24.1%, three in 4.8%, four in 6.6% and ≥5 in 10.9%. In the past decade, 27.8% received DRC, 16.4% R-Bendamustine, 8.9% rituximab monotherapy, 7.7% R-CHOP and the rest varying combinations. 2.2% had received Bortezomib-containing therapy. Before 2010, chlorambucil (21.8%), R-CHOP (10.9%) and FC (9.3%) were the most frequently used first line treatments. BTK-inhibitors have become the most commonly used second line therapy, representing 23% of second line therapy after 2010, reflecting the availability of Ibrutinib on the Cancer Drugs Fund from 2017 and the availability of BTKi trials since 2015. 88 patients had received a BTKi at some point. 118 patients had deceased. Only 30 patients had a cause of death available; this included 7 patients who died from WM itself, 6 from pneumonia, 5 from sepsis (2 were neutropaenic), 3 from HGT, 2 from haemorrhage, 2 from thrombotic events, and 1 from CNS relapse. 5- and 10-year OS rates from diagnosis were 90.5% and 79.4%, with a significant difference in OS rates according to IPSSWM risk at diagnosis (p<0.001, figure 2). There was a trend towards difference in OS rates (P=0.095) according to MYD88 status, with somewhat poorer OS rate amongst MYD88 wild-type patients. CXCR4-status did not impact the OS rate (p=0.93). Conclusions The median age at diagnosis was 64 years, with a third of patients diagnosed under the age of 60. Although diverse, the most frequent indications for treatment in this cohort are hyperviscosity, fatigue and peripheral neuropathy. OS rates are high and correlate with IPSSWM risk, but a majority of patients had received multiple lines of therapy reflecting the chronically relapsing nature of WM. Treatment practices are clearly evolving, with increasing first line use of DRC and R-Bendamustine, as well as BTK inhibitors for relapsed disease. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.
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Tomkins, Oliver, Joshua Bomsztyk, Helen McCarthy, Jaimal Kothari, Dima El-Sharkawi, Charalampia Kyriakou, Guy Pratt, Ali Rismani, and Shirley D'Sa. "An Analysis from the WM UK Rory Morrison Registry - How Does Waldenström's Macroglobulinemia Affect Younger Patients?" Blood 134, Supplement_1 (November 13, 2019): 1543. http://dx.doi.org/10.1182/blood-2019-123693.
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Introduction Waldenström's macroglobulinaemia (WM), an indolent IgM-secreting non-Hodgkin's B-cell lymphoplasmacytic lymphoma, has a reported average age of diagnosis of 65-70 years. and it is often regarded as a disease of the elderly. However, a significant proportion of patients are diagnosed at a younger age and data about this cohort is relatively limited, partly because of the low disease incidence. We seek to further elucidate the characteristics and impact of the disease in the younger patient cohort. Methods The WMUK Rory Morrison Registry (RMR) was searched for all patients younger than 60 years on day of diagnosis. Demographics, disease characteristics, treatment information and survival status were collected retrospectively. Results of patient reported outcome measures (PROMs) were collated. Results 269 patients from 16 UK centres were identified, with years of diagnosis between 1978 and 2018. Analysis focused on 235 patients who fulfilled diagnostic criteria for WM. Patient characteristics are shown in table 1. M:F ratio was 1.61:1 of which 158 patients were Caucasian, 17 Asian, 5 Black, 3 mixed and 6 of other ethnicity, 56 unrecorded. Bone marrow results were available in 156 patients from time of diagnosis, with a median infiltration of 40%. MYD88 L265P was found in 61/74 patients (82.4%) and CXCR4 mutation in 14/39 patients (35.9%). Median Hb was 114/L (range 33-170), platelet count 250x109/L (range 24-689), IgM 19 (range 0-65) and B2-microglobulin 2.7mcg/mL (range 0.5-56.3). The baseline IPSSWM scores were available for 115 patients. 9 patients were anti-MAG antibody positive and 11 had cryoglobulins. Treatment was received by 164 patients (69.8%). The median time from diagnosis to treatment was 2.5 months, range 0-312 months; 69 patients had one line, 32 two lines, 31 three lines, 12 four lines, and 20 five or more lines.14% received R-CHOP as first line therapy, 12.2% DRC,12.2% R-Bendamustine, 7.3% Rituximab monotherapy, 6.7% R-CVP and 6.7% chlorambucil. However, since 2010 DRC and R-Bendamustine were the most frequent. Following first line treatment, 14.7% achieved CR, 55.3% PR or VGPR, 11.9% MR and 14% had SD or PD. At some point in their disease course, high-grade transformation (HGT) was noted in 2 patients and CNS involvement in 10. 30 patients had undergone autologous and six patients allogenic transplantation. Complete, up to date survival information was available for 188 patients, of who 40 patients were deceased (median time from diagnosis 116 months, range 14-451 months). Unfortunately, cause of death was available for only 8 patients at time of analysis, including disease-related in 4, sepsis in 2, HGT in 1 and subdural haemorrhage in 1. One-, 5- and 10-year overall survival (OS) rates were 99.5%, 90% and 81.1%. There was a significant difference in OS according to IPSSWM risk (log rank, P <0.005), with a 5-year OS rate of 92.% for the low risk, 79% for the intermediate, and 38% for the high risk group. There was no significant difference in OS rates according to age group. Of 164 patients asked about their level of disease understanding on a scale of 0-10, the median rating was 0 (average rating 1.85). Only eight patients rated it as 10. Functional information was available for 62 patients, of who 42 (67.7%) had impairment in their ability to go for a walk outside, eight patients (12.9%) required assistance with self-care and one patient (1.6%) was fully dependent on others for personal care. 32 patients (51.6%) needed to spend some or most of their day in a bed or chair. 29 patients (47.8%) had suffered significant financial difficulties because of their diagnosis. Of 59 patients who responded about psychological wellbeing, 36 patients (61%) described feeling depressed. One patient described feeling 'very' depressed, 8 patients 'moderately' depressed and 27 patients 'slightly' depressed. Conclusion A significant proportion of patients with WM are diagnosed under the age of 60 years, and despite its limitations, this retrospective analysis of a large cohort of younger patients illustrates the evolving treatment landscape in the UK. To be expected, WM significant impacts on quality of life and psychological and financial wellbeing in a cohort who would expect to be in work. Encouragingly, OS rates are generally good, although a high IPSSWM risk carries a markedly lower 5-year OS rate also in the younger cohort. A more detailed analysis is underway to explore these issues further. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.
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Doelling, David, Konstantin Khlopenkov, Conor Haney, Rajendra Bhatt, Brent Bos, Benjamin Scarino, Arun Gopalan, and Dante S. Lauretta. "Inter-Calibration of the OSIRIS-REx NavCams with Earth-Viewing Imagers." Remote Sensing 11, no. 22 (November 19, 2019): 2717. http://dx.doi.org/10.3390/rs11222717.
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The Earth-viewed images acquired by the space probe OSIRIS-REx during its Earth gravity assist flyby maneuver on 22 September 2017 provided an opportunity to radiometrically calibrate the onboard NavCam imagers. Spatially-, temporally-, and angularly-matched radiances from the Earth viewing GOES-15 and DSCOVR-EPIC imagers were used as references for deriving the calibration gain of the NavCam sensors. An optimized all-sky tropical ocean ray-matching (ATO-RM) calibration approach that accounts for the spectral band differences, navigation errors, and angular geometry differences between NavCam and the reference imagers is formulated in this paper. Prior to ray-matching, the GOES-15 and EPIC pixel level radiances were mapped into the NavCam field of view. The NavCam 1 ATO-RM gain is found to be 9.874 × 10−2 Wm−2sr−1µm−1DN−1 with an uncertainty of 3.7%. The ATO-RM approach predicted an offset of 164, which is close to the true space DN of 170. The pre-launch NavCam 1 and 2 gains were compared with the ATO-RM gain and were found to be within 2.1% and 2.8%, respectively, suggesting that sensor performance is stable in space. The ATO-RM calibration was found to be consistent within 3.9% over a factor of ±2 NavCam 2 exposure times. This approach can easily be adapted to inter-calibrate other space probe cameras given the current constellation of geostationary imagers.
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Jasik, Agnieszka, Jacek Pruszyński, Ewa Marcinowska-Suchowierska, Monika Puzianowska-Kuźnicka, and Wojciech Stefan Zgliczyński. "The situation of elderly people in Poland in the time of COVID-19." Wiedza Medyczna 4, no. 1 (June 28, 2022): 39–42. http://dx.doi.org/10.36553/wm.130.
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The aim of the article was, to present the situation of old people during the COVID-19 pandemic in Poland. The article has an illustrative character and is based on the available data. Authors starting from the presentation of basic demographic and epidemiological data, discussed such aspects of functioning of the elderly as, physical activity, economic, social, cultural and educational activity, and use of Internet resources, which were transformed due to the COVID-19 pandemic. In particular, isolation and protective measures such as distance, masks, handwashing and stay-at-home policies, and restrictions on congregation, have resulted in significant changes in the daily functioning of the old and have often led to increased social isolation, marginalisation and limited access to health care.
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Szczerbiński, Jakub, Ksawery Szlęzak, Krzysztof Bojakowski, and Piotr Andziak. "Wewnątrznaczyniowe leczenie zwężeń tętnic przeszczepionej allogenicznej nerki." Wiedza Medyczna 4, no. 2 (February 27, 2023): 6–11. http://dx.doi.org/10.36553/wm.140.
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Ostatnie badania kwestionują skuteczność chirurgicznego leczenia zwężenia tętnicy nerkowej. Jednak pacjenci ze zwężeniem tętnicy jedynej nerki mogą odnieść największe korzyści z leczenia wewnątrznaczyniowego. Zwężenie tętnicy nerki przeszczepionej jest przyczyną pogorszenia funkcji narządu, potencjalnie mogącą prowadzić do utraty przeszczepu i zwiększenia śmiertelności w grupie chorych dotkniętych tym powikłaniem. Nie dysponujemy jednak danymi dotyczącymi optymalnego leczenia zwężenia tętnicy nerki przeszczepionej. Obejmuje ono leczenie zachowawcze i ewentualną kwalifikację do leczenia zabiegowego. Przeprowadzenie interwencji wewnątrznaczyniowej daje szansę na korekcję zwężenia i powrót właściwej funkcji nerki przeszczepionej. Podczas operacji wykorzystywane są różne metody - angioplastyka, implantacja stentów, w tym również urządzenia uwalniające miejscowo leki antyproliferacyjne. Obecnie wydaje się, że przeprowadzona w porę interwencja daje takie same szanse na długotrwałe funkcjonowanie przeszczepu i przeżycie, jak w grupie biorców przeszczepu nerki nie rozwijających TRAS. Dane dotyczące epidemiologii, czynników ryzyka i wyników leczenia są skąpe, dlatego potrzebne jest przeprowadzenie dalszych badań.
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Wydra, Arnika, and Izabella Czajka-Oraniec. "The consequences of growth hormone deficiency in adults." Wiedza Medyczna 5, no. 1 (September 22, 2023): 13–18. http://dx.doi.org/10.36553/wm.160.
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Adult growth hormone deficiency (GHD) is a result of the decreased growth hormone (GH) production and secretion from the anterior pituitary gland in adulthood, that cannot be explained by the physiological ageing process. GHD is associated with numerous deleterious consequences such as adverse changes in body composition, carbohydrate and lipid metabolism, alterations in the cardiovascular system, and deterioration in the quality of life (QoL). Most of these complications are at least partially reversible during recombinant human growth hormone (rhGH) replacement therapy. Thus, physicians and particularly endocrinologists, should consider GHD diagnosis and select patients who could benefit from rhGH therapy.
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Szatko, Alicja, Dorota Leszczyńska, Beata Woźniak, and Piotr Glinicki. "The relation between clinical course of pheochromocytoma-paraganglioma (PPGL) and complex genetic etiology." Wiedza Medyczna 5, no. 2 (November 20, 2023): 21–29. http://dx.doi.org/10.36553/wm.150.
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Recent years brought a remarkable progress on understanding the pathophysiology of rare, neuroendocrine tumours– pheochormocytomas and paragangliomas (PPGLs). Approximately 70% PPGLs are associated with germline or somatic mutation in one of more than 25 identified susceptibility genes, which were grouped into three clusters.Cluster 1 includes genes encoding proteins involved in Krebs cycle and hypoxia pathway – cluster 1 related PPGL are usually located extra-adrenally (often manifest as head and neck paragangliomas), they are also characterized by noradrenergic/dopaminergic biochemical phenotype and increased metastatic risk. Cluster 2 encompasses genes involved in kinase signaling pathway, PPGL related to cluster 2 are predominantly pheochromocytomas with adrenergic biochemical phenotype, the patients rarely develop metastases. The least known cluster 3, associated with deregulation of Wnt signaling pathway, includes exclusively somatic mutations leading to aggressive pheochromocytomas.This review summarizes molecular background and the differences between PPGL clusters regarding clinical course, biochemical phenotype, optimal imaging modalities and targeted molecular therapies for metastatic PPGL.
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Dale, David C., Steven P. Treon, David F. McDermott, Diego Cadavid, Xia Luo, Varun Garg, Weihua Tang, et al. "Oral Administration of Mavorixafor, a CXCR4 Antagonist, Increases Peripheral White Blood Cell Counts across Different Disease States." Blood 138, Supplement 1 (November 5, 2021): 2186. http://dx.doi.org/10.1182/blood-2021-152990.
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Abstract Introduction: Peripheral leukocyte deficiency is a common feature of multiple diseases and may render affected individuals susceptible to infections, both common and opportunistic. The CXCR4 chemokine receptor regulates the trafficking of leukocytes among the bone marrow, blood, and lymphatic system (Al Ustwani O, et al. Br J Haematol. 2014;164:15-23). Mavorixafor is an orally available investigational, small-molecule, selective antagonist of the CXCR4 receptor with potential to restore physiological trafficking and maturation of white blood cells (WBCs). Mavorixafor was previously shown to increase totals and subsets of WBCs in healthy volunteers and in a phase 2 clinical trial in adults with WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome (Stone N, et al. Antimicrob Agents Chemother. 2007;51(7):2351-2358; Dale D, et al. Blood. 2020;136(26):2994-3003). Here, we report the effect of daily oral administration of mavorixafor on peripheral WBC counts and subsets in patients with clear cell renal cell carcinoma (ccRCC), WHIM syndrome, and Waldenström's macroglobulinemia (WM). Methods: Percentage changes in total peripheral WBC count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and absolute monocyte count (AMC) from pretreatment levels were evaluated in the following settings: a phase 1/2 trial evaluating mavorixafor (200 mg twice daily or 400 mg once daily [QD]) in combination with axitinib (5 mg twice daily) in patients with advanced ccRCC who received ≥1 prior therapy; a phase 1b trial evaluating mavorixafor (400 mg QD) in combination with nivolumab (240 mg QD) in patients with metastatic ccRCC unresponsive to prior nivolumab monotherapy; a long-term extension of the aforementioned phase 2 trial evaluating mavorixafor 300 or 400 mg QD in patients with WHIM syndrome with pathogenic CXCR4 gain-of-function mutation and ANC ≤400/μL and/or ALC ≤650/μL; and an ongoing phase 1b trial evaluating mavorixafor (200 mg QD for 4 weeks, increased to 400 mg and 600 mg QD thereafter) in combination with ibrutinib (420 mg QD) in patients with WM with MYD88 and CXCR4 mutations. Results: In the study evaluating combination mavorixafor (400 mg QD) and axitinib in ccRCC, total WBC count, ANC, ALC, and AMC increased to 153%, 158%, 143%, and 182% of baseline after 4 weeks (n=49), and with increases sustained at 159%, 171%, 139% and 166% of baseline after 6 months' treatment (n=20). In the study evaluating mavorixafor in combination with nivolumab in ccRCC, total WBC count, ANC, ALC, and AMC increased to 146%, 143%, 141%, and 179% of baseline after 4 weeks (n=9), and with increases sustained at 147%, 136%, 152%, and 191% of baseline after 6 months (n=2). In an interim analysis of the phase 1b trial in WM, compared to screening values, total WBC count, ANC, ALC, and AMC increased to 192%, 170%, 219%, and 186% of baseline after 4 weeks (n=8), and with increases sustained at 163%, 192%, 106%, 172% of baseline after 6 months' (n=5) treatment. In the WHIM syndrome phase 2 extension, total WBC count, ANC, ALC, and AMC increased to 339%, 652%, 239%, and 486% of baseline after 6 months' (n=5) treatment, with annualized infection rate decreasing from 5.6 (SD ± 3.13) events at baseline to 2.2 (SD ± 0.93) events after 40 months. Mavorixafor was generally well tolerated, with manageable safety profile across all indications either alone or in combination with other drugs. Conclusions: Mavorixafor alone or in combination with other therapies is the first oral treatment to either acutely or chronically increase total peripheral WBCs 1.5- to 3-fold and WBC subsets across all disease populations examined, in both the presence (WHIM syndrome and WM) and absence (ccRCC and healthy volunteers) of CXCR4 gain-of-function mutation. Increases in WBC subsets occurred rapidly and were sustained during chronic treatment, with a larger treatment effect in patients with pre-existing cytopenia (WHIM syndrome) compared to patients without cytopenia at baseline (ccRCC and WM). Co-occurring reduction in infection burden was observed in the phase 2 trial in WHIM syndrome. Assessment of the beneficial effects of mavorixafor on total and WBC subsets is ongoing in a phase 3 trial of WHIM syndrome and a phase 1 trial of severe chronic neutropenia (SCN) that will assess the potential to correct cytopenias by elevating total WBC counts. Disclosures Dale: X4 Pharmaceuticals: Consultancy, Honoraria, Research Funding. Treon: AbbVie: Consultancy, Research Funding; Dana Farber Cancer Institute: Current Employment; Self: Patents & Royalties: Holder of multiple patents related to testing and treatment of MYD88 and CXCR4 mutated B-cell malignancies; BMS: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; X4: Research Funding. McDermott: Johnson and Johnson: Consultancy, Honoraria; Genentech: Research Funding; Eisia Inc.: Consultancy, Honoraria; Werewolf Therapeutics: Consultancy, Honoraria; Calithera Biosciences: Consultancy, Honoraria; X4 Pharmaceuticals: Research Funding; Iovance: Consultancy, Honoraria; EMD Serono: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Exelixis: Research Funding; Alkermes, Inc.: Consultancy, Honoraria, Research Funding; Eli Lilly and Company: Consultancy, Honoraria. Cadavid: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Luo: X4 Pharmaceuticals: Consultancy. Garg: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Tang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Jiang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Chen: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Taveras: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bhandari: X4 Pharmaceuticals: Current Employment.
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Moskal, Grzegorz. "Microstructure and Thermal Diffusivity of Micro- and Nano-Sized YSZ." Materials Science Forum 638-642 (January 2010): 900–905. http://dx.doi.org/10.4028/www.scientific.net/msf.638-642.900.
Full textAbstract:
The thermal barrier coatings (TBC) enable to lower temperature (at approx. 170°C) of operating elements in a hot section of gas turbine to a range, which enables to operate for a long time in conditions of high temperature influence and prolongs operation of them even three or four times. Usually, the TBC coverings are constructed of four layers: • superalloys on a base of nickel; • outer ceramic zone, from which low thermal conduction is required. It is, in most cases, ZrO2 oxide stabilized with Y2O3 (YSZ – yttria stabilized zirconia), material of one of lowest values of thermal conductivity in high temperature of a rank 2.3 Wm-1K-1 in 1000°C for 100% density and thermal expansion of a rank 11×10-6°C-1, what enables to reduce thermal stresses. Usually, thickness of an outer ceramic layer is within a range 250-375μm; • bond coat of a type Ni(Co)CrAlY or diffusion layer of a type (Ni,Pt)Al; • layer of barrier oxides, accrueting as a result of temperature growth TGO (thermally grown oxide). In the present study characterization of conventional micro-sized YSZ powders stabilized by 8% of yttria and in comparison nano-sized YSZ will be presented. The tests performed showed that the monoclinic phase content in the nanocrystalline powder is approx. 8.8%, and approx. 7.5% in the conventional powder. The chemical composition analysis and test of powder microstructure were also performed. Carbon, sulphur and gas nitrogen contents were determined and the results received were similar. The surface morphology and powder microstructure on the cross-sections were also characterized. The standard powder with spherical shape and relatively smooth surface is predominant. The internal structure is characterized by the presence of tiny sintered particles and low porosity. The nanocrystalline powder tests showed the presence of particles in the form of tiny polyhedrons with bimodal size distribution of particles (approx. 1μm and 10μm).
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Patterson, Christopher J., Anne Sophie Moreau, Xavier Leleu, Jacob Soumerai, Zachary Hunter, Evdoxia Hatjiharissi, Lian Xu, and Steven Treon. "Abnormalities in Lipoprotein Metabolism Provide Insight into Novel Therapeutic Approaches for Waldenstrom’s Macroglobulinemia (WM)." Blood 108, no. 11 (November 16, 2006): 4749. http://dx.doi.org/10.1182/blood.v108.11.4749.4749.
Full textAbstract:
Abstract WM is an incurable B-cell disorder characterized by the presence of lymphoplasmacytic cells in the bone marrow and an IgM monoclonal protein. The presence of hypocholesterolemia has often been observed in WM patients, though the incidence and significance has not been investigated. As part of these studies, we evaluated lipoprotein levels in 110 patients with WM. The median age for this cohort was 62, and median number of prior therapies was 1. Twenty-one (19.1%) patients were on a lipid-lowering agent (lovastatin, simvastatin, pravastatin). We observed decreased total cholesterol (<160 mg/dL), LDL (<100 mg/dL) and VLDL (<40 mg/dL) levels in 41 (37.3%), 68 (61.8%) and 90 (81.8%) patients, respectively. Among the 41 patients with a cholesterol level of <160 mg/dL, only 7 patients were on a lipid lowering agent. Importantly, median serum IgM levels which serve as a surrogate marker for WM disease burden were higher among patients with hypocholesterolemia (3440 vs. 1587 mg/dL; p=0.0004). Moreover, significantly lower levels of serum IgM (885 vs. 1960 mg/dL; p=0.004) were observed among patients on a lipid-lowering agent. Given these results, which suggested a possible disease dependency on cholesterol metabolism, as well as possible anti-tumor effect of statins, we explored the impact of two statins (lovastatin, simvastatin) on the growth and survival of BCWM.1 WM cells. The studies demonstrated that both lovastatin and simvastatin inhibited proliferation (by MTT assay), and induced apoptosis (by Annexin-PI assay) in a dose dependent manner (0.5–50 um) at concentrations that overlapped pharmacologically achievable levels. Taken together, these studies suggest that lipoprotein metabolism may be essential for WM growth and survival, and that statin agents may represent clinically useful agents for the treatment of WM.
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Gutierrez, Norma C., Roberto JP Magalhaes, Ramón García-Sanz, María-Belén Vidriales, Enrique M. Ocio, Bruno Paiva, Daniel del Carpio, et al. "Fluorescence In Situ Hybridization (FISH) Analysis In 160 Patients with IgM Monoclonal Gammopathies." Blood 116, no. 21 (November 19, 2010): 1916. http://dx.doi.org/10.1182/blood.v116.21.1916.1916.
Full textAbstract:
Abstract Abstract 1916 IgM monoclonal gammopathies are a heterogeneous group of clonal B-cell disorders that include indolent forms - IgM monoclonal gammopathy of undetermined significance (IgM-MGUS) and asymptomatic Waldenström macroglobulinemia (aWM) - as well as symptomatic WM. Similarly to what has been hypothesized in plasma cell disorders, the mechanism leading to the malignant transformation of indolent IgM-MGUS and a-WM to symptomatic WM could underlie evolving cytogenetic abnormalities. However, cytogenetic abnormalities have been mainly explored in patients with WM, while this information in IgM-MGUS and aWM patients is still scanty. In the present study we have analyzed the frequency and prognostic impact of genetic changes as detected by FISH in a series of 161 newly diagnosed patients with an IgM monoclonal gammopathy. Median follow-up in the overall series was of 31 months. Patients were diagnosed with an IgM-MGUS (n=31), a-WM (n=50) and WM (n=80) according to the 2002 WM consensus group criteria. FISH analysis was performed on immunomagnetically enriched bone marrow B-cells to ascertain the following chromosomal abnormalities: 6q and retinoblastoma (Rb) deletions, as well as the IGH translocations t(4;14), t(11;14) and t(14;16). Table 1summarizes the frequency of cytogenetic abnormalities detected in the overall series of patients. Interestingly, the proportion of patients with 6q deletion significantly increased (p=.002) from IgM-MGUS (0%) to a-WM (12%) and WM (28%). The frequency of Rb deletion was generally low, and only detected in a-WM (4%) and WM (2%) patients, while absent in IgM-MGUS cases (0%). In turn, the frequency of IGH translocations was superior in IgM-MGUS (6%) and a-WM (8%) compared to WM (1%) patients. Interestingly, t(11;14) represented 50% of all translocations in IgM-MGUS and a-WM but not in WM. By contrast t(4;14) and t(14;16) were undetectable in the overall series of patients. According to the frequency of 6q deletions and its evolving pattern, we further explored if this specific cytogenetic abnormality had an impact on patients outcome. In patients with symptomatic WM the presence of 6q deletion do not showed an impact on patients progression-free survival (p=.5) and overall survival (p=.8). However, in the group of patients with a-WM those harboring a 6q deletion vs. no 6q deletion showed a significantly increased risk of progression to symptomatic disease: median time to progression - TTP- of 37 vs. 145 months, respectively (p=.002) and 3-year TTP rates of 67% vs. 100%, respectively (p=.002). In summary, these results suggest that the presence of 6q deletion may be a secondary event associated with the malignant transformation of indolent IgM-MGUS to a-WM and symptomatic WM. Accordingly, routine screening of 6q deletion in patients with a-WM may help to identify a subgroup with higher risk of progression. Disclosures: No relevant conflicts of interest to declare.
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Sobolewski, Piotr, Klaudia Dopytalska, Marek Roszkiewicz, Agata Mikucka-Wituszyńska, Elżbieta Szymańska, and Irena Walecka. "Cutaneous and mucosal melanoma." Wiedza Medyczna 1, no. 1 (August 13, 2019): 1–3. http://dx.doi.org/10.36553/wm.12.
Full textAbstract:
Malignant melanoma (MM) still remains a potentially fatal disease despite the fact that advanced diagnostic methods and modern therapeutic options are available. Melanoma is a cancer deriving from neuroectodermal melanocytic cells. The standardized incidence rate of melanoma in Poland is 4,9 per 100 000. The mucosal melanoma is a rare form of this cancer accounting for only 2% of the diagnosed cases. The fast diagnosis and surgical treatment are the keys to decreased mortality. In metastatic disease systemic therapy is needed but no highly efficient drug has been identified yet. This paper concentrates on introduction of elemental knowledge about melanoma to raise awareness among medical professionals of different specialities in order not to overlook any case of melanoma.
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Pavlakis, K. G., D. Hatzidimitriou, E. Drakakis, C. Matsoukas, A. Fotiadi, N. Hatzianastassiou, and I. Vardavas. "ENSO surface longwave radiation forcing over the tropical Pacific." Atmospheric Chemistry and Physics Discussions 6, no. 6 (December 11, 2006): 12895–928. http://dx.doi.org/10.5194/acpd-6-12895-2006.
Full textAbstract:
Abstract. We have studied the spatial and temporal variation of the surface longwave radiation (downwelling and net) over a 21-year period in the tropical and subtropical Pacific Ocean (40 S–40 N, 90 E–75 W). The fluxes were computed using a deterministic model for atmospheric radiation transfer, along with satellite data from the ISCCP-D2 database and reanalysis data from NCEP/NCAR (acronyms explained in main text), for the key atmospheric and surface input parameters. An excellent correlation was found between the downwelling longwave radiation (DLR) anomaly and the Niño-3.4 index time-series, over the Niño-3.4 region located in the central Pacific. A high anti-correlation was also found over the western Pacific (15–0 S, 105–130 E). There is convincing evidence that the time series of the mean downwelling longwave radiation anomaly in the western Pacific precedes that in the Niño-3.4 region by 3–4 months. Thus, the downwelling longwave radiation anomaly is a complementary index to the SST anomaly for the study of ENSO events and can be used to asses whether or not El Niño or La Niña conditions prevail. Over the Niño-3.4 region, the mean DLR anomaly values range from +20 Wm−2 during El Niño episodes to –20 Wm−2 during La Niña events, while over the western Pacific (15–0 S, 105–130 E) these values range from –15 Wm−2 to +10 Wm−2, respectively. The long- term average (1984–2004) distribution of the net surface longwave radiation to the surface over the tropical and subtropical Pacific for the three month period November-December-January shows a net thermal cooling of the ocean surface. When El Niño conditions prevail, the thermal radiative cooling in the central and south-eastern tropical Pacific becomes weaker by 10 Wm−2 south of the equator in the central Pacific (7–0 S, 160–120 W) for the three-month period of NDJ, because the DLR increase is larger than the increase in surface thermal emission. In contrast, the thermal radiative cooling over Indonesia is enhanced by 10 Wm−2 during the early (August–September–October) El Niño phase.
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Pavlakis, K. G., D. Hatzidimitriou, E. Drakakis, C. Matsoukas, A. Fotiadi, N. Hatzianastassiou, and I. Vardavas. "ENSO surface longwave radiation forcing over the tropical Pacific." Atmospheric Chemistry and Physics 7, no. 8 (April 24, 2007): 2013–26. http://dx.doi.org/10.5194/acp-7-2013-2007.
Full textAbstract:
Abstract. We have studied the spatial and temporal variation of the surface longwave radiation (downwelling and net) over a 21-year period in the tropical and subtropical Pacific Ocean (40 S–40 N, 90 E–75 W). The fluxes were computed using a deterministic model for atmospheric radiation transfer, along with satellite data from the ISCCP-D2 database and reanalysis data from NCEP/NCAR (acronyms explained in main text), for the key atmospheric and surface input parameters. An excellent correlation was found between the downwelling longwave radiation (DLR) anomaly and the Niño-3.4 index time-series, over the Niño-3.4 region located in the central Pacific. A high anti-correlation was also found over the western Pacific (15–0 S, 105–130 E). There is convincing evidence that the time series of the mean downwelling longwave radiation anomaly in the western Pacific precedes that in the Niño-3.4 region by 3–4 months. Thus, the downwelling longwave radiation anomaly is a complementary index to the SST anomaly for the study of ENSO events and can be used to asses whether or not El Niño or La Niña conditions prevail. Over the Niño-3.4 region, the mean DLR anomaly values range from +20 Wm−2 during El Niño episodes to −20 Wm−2 during La Niña events, while over the western Pacific (15–0 S, 105–130 E) these values range from −15 Wm−2 to +10 Wm−2, respectively. The long- term average (1984–2004) distribution of the net downwelling longwave radiation at the surface over the tropical and subtropical Pacific for the three month period November-December-January shows a net thermal cooling of the ocean surface. When El Niño conditions prevail, the thermal radiative cooling in the central and south-eastern tropical Pacific becomes weaker by 10 Wm−2 south of the equator in the central Pacific (7–0 S, 160–120 W) for the three-month period of NDJ, because the DLR increase is larger than the increase in surface thermal emission. In contrast, the thermal radiative cooling over Indonesia is enhanced by 10 Wm−2 during the early (August–September–October) El Niño phase.
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MURTHY, B. S., and S. SIVARAMAKRISHNAN. "Surface fluxes over Goa during Indian monsoon." MAUSAM 56, no. 1 (January 19, 2022): 251–56. http://dx.doi.org/10.54302/mausam.v56i1.900.
Full textAbstract:
Variation of surface sensible heat flux over the west coast in the premises of National Center for Antarctic and Ocean Research (NCAOR), Vasco-da-Gama (15° 21' N, 73° 51' E), Goa during Offshore trough (phase-I) and Warm pool campaigns (phase-II) of ARMEX is studied. Sensible heat flux as measured by sonic anemometer at 5 m above surface is -50 to 150 Wm-2 during 13-28 July, 2002 (phase I) and -5 to 350 Wm-2 during 21-24 April, 2003 (phase II). Coastal atmospheric surface layer at Goa during night time is found to be near neutral (nearly zero heat flux) in April 2003 whereas stable (negative heat flux) in July 2002. All components of solar radiation measured by Eppley radiometers at 2 m above surface are used to compute net radiation which is 900 Wm-2 at noon in April 2003. Net solar radiation is nearly equal to incoming short wave radiation during daytime as net long wave radiation (100 Wm-2) compensates the loss due to reflection of short wave radiation (-100 Wm-2) by the ground. High winds in the surface layer are observed during late night hours with calm winds around sunrise and after sunset giving rise to two minima in the diurnal curve. Influence of sea-breeze on the surface layer over land is discussed.
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Santos, Daniel Ditzel, Olivier Tournilhac, Lian Xu, Hatjiharrisi Evdoxia, Zachary Hunter, Andrew Branagan, Robert Manning, Kenneth C. Anderson, Iqbal Grewal, and Steven P. Treon. "B-Lymphocyte Stimulator Protein (BLYS) Is Expressed by Bone Marrow Mast and Lymphoplasmacytic Cells in Waldenstrom’s Macroglobulinemia, and Provides Signaling for Growth, Survival and IgM Secretion." Blood 104, no. 11 (November 16, 2004): 3358. http://dx.doi.org/10.1182/blood.v104.11.3358.3358.
Full textAbstract:
Abstract B-lymphocyte stimulator protein (BLYS) is a member of the tumor necrosis family of ligands which is expressed by monocytes and neutrophils and regulates B-cell homeostasis and immunoglobulin production through its receptors BCMA, TACI and BAFF-R. In recent studies, we have shown that bone marrow (BM) mast cells (MC) are increased in WM patients and support tumor cell growth. We therefore evaluated sorted WM BM MC (CD117+FceRI+) and lymphoplasmacytic cells (LPC) for BLYS, BCMA, TACI AND BAFF-R by multicolor flow cytometry and RT-PCR. Results were as follows: Flow Cytometry RT-PCR WM MC WM MC BLYS 5/7 (71%) 8/15 (53%) 25/26 (96%) 20/23 (61%) BCMA 4/6 (66%) 7/8 (87%) 20/20 (100%) 8/13 (61%) TACI 15/16 (93%) 7/7 (100%) 20/20 (100%) 12/15 (80%) BAFF-R 11/16 (68%) 5/8 (62%) 20/20 (100%) 11/11 (100%) By RT-PCR, BLYS was detected in MC from 5/7 normal donors. However, in contrast to MC from WM patients, BLYS was not expressed on the cell surface of MC from 7 normal donors using multicolor flow cytometry (p=0.02). Importantly, recombinant human BLYS stimulated proliferation, enhanced survival and/or induced IgM secretion of WM LPC at concentrations of up to 1 ug/mL. Paradoxically, at higher concentrations (5, 10 ug/mL) BLYS induced apoptosis of WM LPC. These studies therefore demonstrate that MC and LPC in WM patients express BLYS and BLYS receptors, and provide the framework for specific targeting of MC-LPC interactions in WM.
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Bristow, Michael S., Jessica E. Simon, Robert A. Brown, Michael Eliasziw, Michael D. Hill, Shelagh B. Coutts, Richard Frayne, Andrew M. Demchuk, and J. Ross Mitchell. "MR Perfusion and Diffusion in Acute Ischemic Stroke: Human Gray and White Matter have Different Thresholds for Infarction." Journal of Cerebral Blood Flow & Metabolism 25, no. 10 (May 11, 2005): 1280–87. http://dx.doi.org/10.1038/sj.jcbfm.9600135.
Full textAbstract:
It is thought that gray and white matter (GM and WM) have different perfusion and diffusion thresholds for cerebral infarction in humans. We sought to determine these thresholds with voxel-by-voxel, tissue-specific analysis of coregistered acute and follow-up magnetic resonance (MR) perfusion- and diffusion-weighted imaging. Quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion coefficient (ADC) maps were analyzed from nine acute stroke patients (imaging acquired within 6 h of onset). The average values of each measure were calculated for GM and WM in normally perfused tissue, the region of recovered tissue and in the final infarct. Perfusion and diffusion thresholds for infarction were determined on a patient-by-patient basis in GM and WM separately by selecting thresholds with equal sensitivities and specificities. Gray matter has higher thresholds for infarction than WM ( P<0.009) for CBF (20.0 mL/100 g min in GM and 12.3 mL/100 g min in WM), CBV (2.4 mL/100 g in GM and 1.7 mL/100 g in WM), and ADC (786 × 10−6 mm2/s in GM and 708 × 10−6 mm2/s in WM). The MTT threshold for infarction in GM is lower ( P = 0.014) than for WM (6.8 secs in GM and 7.1 secs in WM). A single common threshold applied to both tissues overestimates tissue at risk in WM and underestimates tissue at risk in GM. This study suggests that tissue-specific analysis of perfusion and diffusion imaging is required to accurately predict tissue at risk of infarction in acute ischemic stroke.
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Ioakimidis, Thea, Christopher J. Patterson, Zachary Hunter, Jacob Soumerai, Robert Manning, Diane L. Warren, Irene Ghobrial, Patricia Sheehy, and Steven Treon. "Cholesterol Regulation and Statin Therapy in Patients with Waldenstrom's Macroglobulinemia." Blood 114, no. 22 (November 20, 2009): 4789. http://dx.doi.org/10.1182/blood.v114.22.4789.4789.
Full textAbstract:
Abstract Abstract 4789 Patients with WM commonly display low cholesterol levels, particularly LDL and VLDL levels. Given these observations, we examined their levels in 110 patients with WM, and observed decreased total cholesterol (<160 mg/dL), LDL (<100 mg/dL) and VLDL (<40 mg/dL) levels in 41 (37.3%), 68 (61.8%) and 90 (81.8%) patients, respectively. Importantly, median serum IgM levels which serve as a surrogate marker for WM disease burden were higher among patients with hypocholesterolemia (3440 vs. 1587 mg/dL; p=0.0004). Longitudinal follow-up of progressing as well as responding patients demonstrated an inverse correlation between serum IgM and cholesterol levels, which was not an artifact of laboratory testing. Importantly, significantly lower serum IgM levels (885 vs. 1960 mg/dL; p=0.004) were observed among those patients who were on a statin lipid-lowering agent. We therefore investigated the in vitro potential of statins to mediate anti-WM activity and showed that simvastatin acted a potent inducer of WM cell apoptosis through inhibition of geranylgeranylated proteins. Given these observations, we investigated the potential of simvastatin to suppress disease progression in WM patients with slowly progressing disease who would otherwise have been on watch and wait. Patients and Methods Eighteen patients, 8 of whom were previously untreated, and who were asymptomatic with slowly progressing disease were enrolled in this study. The median age for these patients was 67 (range 42-88 years), median IgM was 2,610 (571-5,880 mg/dL), and median hematocrit was 35.4 (range 30.2-41.4%). Patients received Simvastatin at 20 mg daily for the first week, then dose escalated weekly by 20 mg a day to a maximum of 80 mg daily by week 4. Patients were maintained on therapy until progression. Results With a median follow-up of 6 months (range 3-18 months), 7 patients have demonstrated objective disease progression. No objective responses have been observed in any treated patients. Among non-progressing patients, serum IgM levels (2,610 vs. 2545 mg/dL) and hematocrit (35.4% vs. 34.5%) remain stable (p=NS). Grade 2 toxicities included elevation in CPK (n=1), and musculoskeletal pain (n=3). No grade 3 toxicities were observed. Conclusions Simvastatin does not produce objective responses in patients with WM, though may have potential for suppression of disease progression in some patients with WM. Disclosures: No relevant conflicts of interest to declare.
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Hivert, Benedicte, Claudine Caron, Stephanie Petit, Cecile Charpy, Corinne Fankam-Siaka, Stephanie Lecocq, Christophe Zawadzki, et al. "Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenström macroglobulinemia." Blood 120, no. 16 (October 18, 2012): 3214–21. http://dx.doi.org/10.1182/blood-2011-11-388256.
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AbstractAcquired von Willebrand syndrome is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive patients with WM showed a negative relation between VWF levels < 130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo < 50 U/dL (< 40 for patients with blood group O) fulfilled the acquired von Willebrand syndrome criteria. They had higher mIgMC and viscosity. Reduction in mIgMC was associated with increase in VWF levels. The low VWF:RCo/VWF:Ag ratio suggested that high viscosity might be associated with increased shear force and cleavage of multimers. Surprisingly, 43 patients (59%) presented with high VWF:Ag (> 110 U/dL). They had higher bone marrow microvessel density and vascular endothelial growth factor expression on bone marrow mast cells. Five-year survival rates of patients with VWF:Ag < 110, between 110 and 250, and more than 250 U/dL were 96%, 71%, and 44%, respectively (P < .0001). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (P < .0001), independently of the international scoring system. These results support systematic assessment of VWF in patients with WM. The adverse prognostic value of high VWF levels raises issues on interactions between lymphoplasmacytic cells, mast cells, and endothelial cells in WM.
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Hale, Erica Rosenberger, David C. Goff, Scott Isom, Caroline Blackwell, Melicia C. Whitt-Glover, and Jeffery A. Katula. "Relationship of Weekly Activity Minutes to Metabolic Syndrome in Prediabetes: The Healthy Living Partnerships to Prevent Diabetes." Journal of Physical Activity and Health 10, no. 5 (July 2013): 690–98. http://dx.doi.org/10.1123/jpah.10.5.690.
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Background:Physical inactivity contributes to metabolic syndrome (MetS) in overweight/obesity. However, little is known about this relationship in prediabetes.Methods:The study purpose is to examine relationships between physical activity (PA) and MetS in prediabetes. The Healthy Living Partnerships to Prevent Diabetes tested a community translation of the Diabetes Prevention Program (DPP). Three hundred one overweight/obese prediabetics provided walking minutes/week (WM) and total activity minutes/week (AM) via the International Physical Activity Questionnaire. MetS was at least 3 of waist (men ≥ 102 cm, women ≥ 88 cm), triglycerides (≥150 mg·dl), blood pressure (≥130·85 mm Hg), glucose (≥100mg·dl), and HDL (men < 40mg·dl, women < 50mg·dl).Results:The sample was 57.5% female, 26.7% nonwhite/Hispanic, 57.9 ± 9.5 years and had a body mass index (BMI) 32.7 ± 4 kg·m2. Sixty percent had MetS. Eighteen percent with MetS reported at least 150 AM compared with 29.8% of those without MetS. The odds of MetS was lower with greater AM (Ptrend = .041) and WM (Ptrend = .024). Odds of MetS with 0 WM were 2.08 (P = .046) and with no AM were 2.78 (P = .009) times those meeting goal. One hour additional WM led to 15 times lower MetS odds.Conclusions:Meeting PA goals reduced MetS odds in this sample, which supported PA for prediabetes to prevent MetS.
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Leszczyńska, Dorota, Agata Tuszyńska, Magdalena Zgliczyńska, Wojciech Zgliczyński, and Waldemar Misiorowski. "An effect of single high dose of vitamin D3 on the risk of nosocomial infections, hospitalization time and mortality in hospitalized elderly population. A preliminary report." Wiedza Medyczna 2, no. 2 (December 8, 2020): 1–5. http://dx.doi.org/10.36553/wm.56.
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Introduction: Observational studies indicate a significant impact of serum 25(OH)D concentration on incidence of hospital-acquired infections. However, we did not find any interventional study assessing the effect of vitamin D3 administration at the admission on the course of further hospitalization in internal medicine departments.
Objective of the paper: Investigation of the impact of one-time high-dose vitamin D3 administration in elderly patients on the day of urgent admission to the hospital, on hospital-acquired infections.
Materials and methods: A randomized, two-arms, open pilot study in 97 adults aged 60-100. A study group was given a single dose of 60,000 IU vitamin D3 and a control group was not subject to any intervention. Serum 25(OH)D and calcium were measured at the baseline and after 7 days.
Results: 77.32% of studied patients were vitamin deficient, and among those, in 28.87% severe vitamin D deficiency was found. After single administration of 60,000 IU of vitamin D3, only 4 patients achieved recommended serum 25(OH)D concentration. The highest increase in serum 25(OH)D was observed in patients with severe deficiency. Numbers of observed nosocomial infections such as flu, hospital-acquired pneumonia or Klebsiella pneumoniae MBL+ infection did not differ significantly between study and control group, however there was a trend close to significance for lower incidence of Clostridium difficile infection in the vitamin D3 group.
Conclusions: Preliminary results of the presented research indicate possible protective effect of single high dose of vitamin D3 against Clostridium difficile infection during hospitalization. Further research on larger group of patients, using higher dose of vitamin D3 is necessary.
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Tomović, Vladimir M., Radoslav Šević, Marija Jokanović, Branislav Šojić, Snežana Škaljac, Tatjana Tasić, Predrag Ikonić, Mateja Lušnic Polak, Tomaž Polak, and Lea Demšar. "Quality traits of <i>longissimus lumborum</i> muscle from White Mangalica, Duroc × White Mangalica and Large White pigs reared under intensive conditions and slaughtered at 150 kg live weight: a comparative study." Archives Animal Breeding 59, no. 3 (September 27, 2016): 401–15. http://dx.doi.org/10.5194/aab-59-401-2016.
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Abstract. To compare quality traits of longissimus lumborum muscle of three genotypes, 20 White Mangalica (WM), 20 crossbred Duroc × White Mangalica (DWM) and 20 Large White (LW) pigs were allotted to the same indoor rearing and feeding conditions. Crossbred and LW pigs grew faster than WM pigs reaching 150 kg on average 168 and 288 days before WM, respectively. Meat from WM pigs had the highest intramuscular fat content and darkest and reddest colour; crosses were at an intermediate position, with significant differences among all genotypes. In addition, ultimate pH, water-holding capacity and iron content were significantly the highest in meat from WM pigs, compared to the other two genotypes. Crossing WM with Duroc had a significant effect on individual fatty acid content of meat. However, the sum of saturated, monounsaturated and polyunsaturated fatty acids remained unchanged. WM and DWM pigs had significantly more tender meat than LW pigs. Monounsaturated fatty acids (MUFAs) were most abundant, followed by saturated (SFAs) and polyunsaturated fatty acids (PUFAs) in meat from all animals. Meat from WM and DWM pigs had a significantly higher percentage of MUFAs and significantly lower percentage of SFAs than LW pigs.
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Giné, Eva, Jordina Rovira, Alejandra Martinez-Trillos, Neus Villamor, Antonio Martinez, Gonzalo Gutierrez-Garcia, Luis Colomo, et al. "Initial Features and Outcome Are Similar in Patients with Lymphoplasmacytic Lymphoma Regardless They Meet or Not Criteria of Waldenström Macroglobulinemia,." Blood 118, no. 21 (November 18, 2011): 3677. http://dx.doi.org/10.1182/blood.v118.21.3677.3677.
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Abstract Abstract 3677 Lymphoplasmacytic lymphoma (LPL) is a very heterogeneous disease from the clinical stand point, including the fact that Waldenström macroglobulinemia (WM) can be recognized in a significant proportion of LPL cases. Whether LPL with and without criteria for WM differ in the clinical features and outcome is not well known and is the aim of the present study. For this purpose, 50 patients (median age, 67 years (range, 19 to 91; 50% males) with a tissue biopsy diagnostic of LPL or a bone marrow infiltration by LPL were included in the present study. Main clinic-biological characteristics and outcome were recorded and analysed. Bone marrow infiltration and presence of a serum paraprotein were observed in 42 cases (89%) and 37 cases (86%), respectively. WM according to WHO criteria was identified in 26 patients (60%). Thirty-four patients received treatment for LPL (69%), including rituximab at any time in 74% of treated patients. The main clinical features of the series according to the WM/LPL or non-WM/LPL criteria are listed in the table. No relevant differences were identified when comparing WM cases with remaining LPL cases, except for those determined by their definition. Six patients eventually developed solid neoplasms with no differences between both groups. After a median follow-up of 35 months (range 0,3 to 209), 17 patients have died, including 10 patients by disease progression, 2 by secondary malignancies, 2 by heart failure, and 3 by unknown causes. The median survival of the whole series was 133 months (CI 95%: 40–226). Among the ten patients who died as a result of disease progression, two different patterns were observed. In six cases disease progression was characterized by general symptoms and lymph node growth, whereas the other 4 cases showed severe cytopenias unresponsive to treatment. These patterns were both observed indistinctly in WM and the non-WM/LPL cases. OS was similar in both groups of patients (median OS 133 vs. 216 months in WM and non-WM, respectively; p=NS). In conclusion, no major differences were observed in terms of initial features and outcome among LPL patients according to the definition of WM or non-WM/LPL.FeaturesAll patients (n=50)WM/LPL patients (n=26)Non-WM /LPL patients (n= 24)Age (median, yrs)676668Gender (male, %)25 (50%)12 (46%)13 (54%)Stage IV (%)46 (94%)26 (100%)20 (87%)Bone marrow infiltration44 (90%)26 (100%)*18 (78%)*Serum paraprotein37 (86%)26 (100%)*11 (65%)*IgM type30 (81%)26 (100%)*4 (36%)*M size (median, g/L)181815.3ECOG ≥ 2 (%)8 (18%)2 (9%)6 (29%)Enlarged lymph nodes17 (37%)8 (33%)9 (41%)Splenomegaly12 (26%)5 (20%)7 (33%)Bulky disease7 (15%)3 (12%)4 (18%)Hb (<100 g/L)14 (29%)8 (31%)6 (27%)Platelet (<100x 109/L)6 (13%)4 (15%)2 (10%)High serum LDH6 (13%)3 (12%)3 (15%)High serum beta-2-m19 (50%)10 (48%)9 (53%)No initial treatment21 (43%)13 (50%)8 (35%)# Treatments (median, range)2 (1–7)3 (1–7)*1 (1–4)*60-month overall survival (%)67% (51–83%)71% (51–91%)65% (41–89%)Significant p values for WM vs. non-WM*: bone marrow infiltration (p=.018), serum paraprotein (p=.002), IgM type (p=<.001), lines of treatment (p=.004). Disclosures: No relevant conflicts of interest to declare.
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Paiva, Bruno, Maria-Carmen Montes, Ramón García-Sanz, Jennifer Alonso, Natalia de las Heras, Fernando Escalante, Alfonso Garcia de Coca, et al. "Multiparameter Flow Cytometry (MFC) for Identification of the Waldenström's Clone in IgM MGUS and Waldenstrom's Macroglobulinemia (WM): New Criteria for Differential Diagnosis and Risk Stratification." Blood 120, no. 21 (November 16, 2012): 936. http://dx.doi.org/10.1182/blood.v120.21.936.936.
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Abstract Abstract 936 Demonstration of bone marrow (BM) infiltration by lymphoplasmacytic lymphoma is essential to the diagnosis of WM, and a trephine biopsy is considered mandatory for this assessment. Multiparameter flow cytometry (MFC) has demonstrated its clinical relevance in MGUS and myeloma; however, immunophenotypic studies on IgM monoclonal gammopathies are scanty, and focus only in patients with WM. Herein, MFC immunophenotyping was performed on BM samples from 244 patients, including 67 IgM MGUS, 77 smoldering, and 100 symptomatic WM newly diagnosed patients according to the Second International Workshop. A four color panel that systematically allowed the identification of B cells and plasma cells (PC), and their phenotypic characterization for a total of 24 antigens was used. We first analyzed the percentage of B cells and PC in BM and the percentage of light chain restricted cells in both compartments. Our results show a progressive increment of B cells from IgM MGUS to smoldering and symptomatic WM (medians of 2%, 9% and 12%; P<.001), as well of light chain restricted B cells (75%, 96% and 99%; P<.001). In contrast, no differences were found for the percentage of PC (median of 0.3%), but light chain restricted PC progressively increased from IgM MGUS to smoldering and symptomatic WM (70%, 85% and 97%; P<.001). Accordingly, only 1% of IgM MGUS patients showed >10% B cells, in contrast to 34% and 55% of smoldering and symptomatic WM (P<.001). Likewise, only 1% of IgM MGUS patients showed 100% light chain restricted B cells, in contrast to 19% and 40% of smoldering and symptomatic WM (P<.001); similar results being also found using a cutoff of 100% light chain restricted PC. Subsequently, we explored whether the percentages of BM and light chain restricted B cells and PC could predict time to progression (TTP) from smoldering into symptomatic WM, as well as overall survival (OS) in symptomatic WM. In smoldering WM, B cells (>10% vs ≤10%: median TTP of 47m vs 145m; P=.016) and light chain restricted B cells (100% vs <100%: 26m vs 145m; P<.001) but not PC, predicted risk of progression. On the multivariate analysis that included serum M-spike (±3g/dL), BM infiltration (±50% lymphoplasmacytic cells), BM B-cells and light chain restricted B cells (by MFC), only the later retained independent prognostic value (HR: 19.8, P=.001). Upon analyzing factors influencing survival in symptomatic WM patients, cases with >10% B cells showed a trend for inferior OS (P=.080), and significant differences emerged when comparing patients with 100% vs <100% light chain restricted B cells (median OS 44m vs 78m; P=.001). The later marker was independent (HR: 2.6; P=.004) of the International Prognostic Scoring System (HR: 2.2; P=.006). Focusing on the antigenic profiles of B cells and PC, we noted that within the B-cell compartment there was a progressive increment of CD22dim (69%, 92% and 88%; P<.001), CD25+ (61%, 88% and 90%; P<.001) and sIgM+ (88%, 95% and 97%; P=.002) B cells from IgM MGUS to smoldering and symptomatic WM. This underlies that the accumulating light chain restricted clonal B cells show a characteristic Waldenstrom's phenotype (CD22dim/CD25+/IgM+). Of note, a bimodal (from - to +) expression for the B cell memory marker CD27 was found in >50% of WM patients, which raises the possibility that the WM clone may arise, at least in some cases, before antigenic stimulation; subsequent maturation of the clone into PC would explain the typical presence of somatic hypermutations. On the other hand, B-cells from IgM MGUS and WM patients were negative in ≥90% of cases for CD5, CD10, CD11c and CD103, which can be useful to differentiate between WM and other B-NHL. Finally, the antigenic profile of PC in IgM MGUS and WM was similar to that of normal PC, and different from myeloma PC by consistently showing a CD27+ and CD56- phenotype, in addition to sIgM+ expression in ≥87% of all cases. Similarly to B-cells, we also noted that within the PC compartment there was a progressive increment of CD19+, CD45+ and sIgM+ CD20+ PC from IgM MGUS to smoldering and symptomatic WM. This underlies that this transition is asssociated with an accumulation of light chain restricted clonal PC displaying an immature/plasmablastic phenotype. In summary, our results highlight the potential value of MFC immunophenotyping for the characterization of the Waldenström's clone, as well as for the differential diagnosis, risk of progression and survival in WM. Disclosures: No relevant conflicts of interest to declare.
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Phyu, Po, Aine Merwick, Indran Davagnanam, Fay Bolsover, Fatima Jichi, Claudia Wheeler-Kingshott, Xavier Golay, et al. "Increased resting cerebral blood flow in adult Fabry disease." Neurology 90, no. 16 (March 21, 2018): e1379-e1385. http://dx.doi.org/10.1212/wnl.0000000000005330.
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ObjectiveTo assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3.MethodsThis cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3.ResultsThe mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78–31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08–24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72–27.12] vs 16.25 mL/100 mL/min [95% CI 14.03–18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85–43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57–42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume (r = 0.59, p = 0.006), not with plasma lyso-Gb3.ConclusionIn FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury.
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Rosales-Nieto, C. A., H. G. Gamez-Vazquez, J. Gudino-Reyes, E. A. Reyes-Ramirez, M. Eaton, R. L. Stanko, C. A. Meza-Herrera, and A. Gonzalez-Bulnes. "Nutritional and metabolic modulation of the male effect on the resumption of ovulatory activity in goats." Animal Production Science 51, no. 2 (2011): 115. http://dx.doi.org/10.1071/an10124.
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The present study evaluated possible modulation of the buck effect by nutritional and metabolic cues during the transition to the breeding season in adult goats with divergent bodyweight (BW) and body condition (BCS) at 27°N. In mid-February, goats (Boer × Spanish, n = 32) were assigned to receive one of the following two experimental diets to fulfill different allowances of nutritional requirements: (1) 100% (n = 16; BW = 52.3 ± 1.5 kg, BCS = 1.6 ± 0.1 units; T-100) or (2) 150% (n = 16; BW = 60.9 ± 2.4 kg, BCS = 1.6 ± 0.1 units; T-150) from February to August. Blood samples were collected to analyse thyroxine (T4), triiodothyronine (T3), non-esterified fatty acids (NEFA), triglycerides (Tg) and progesterone (P4). Final BW and BCS favoured (P < 0.001) the T-150 group (74.9 ± 2.8 v. 56.3 ± 1.4 kg, and 4.4 ± 0.2 v. 1.9 ± 0.1 units, respectively). However, mean values for NEFA, Tg, T3 and T4 did not differ (P > 0.05) between the experimental groups. Thereafter, in early August, half of the does in each diet treatment were randomly selected for determining the response to the ‘male effect’ (WM), forming the following two treatment groups: (1) T-100-WM (n = 8), or (2) T-150-WM (n = 8); the remaining does formed two groups without male exposure (WOM), as follows: (3) T-100-WOM (n = 8) and (4) T-150-WOM (n = 8). To evaluate ovarian activity, blood samples were collected from all does on Days 2–4 during the 14-day period after the male exposure. On Day 12, all does exposed to males (16/16), irrespective of the nutritional treatment, depicted ovulatory activity, whereas only 3/16 (18.75%) T-WOM does did, indicating a significant (P < 0.001) difference between these treatment groups. The increased nutritional level of the T-150 group during the anoestrous season did not result in an early onset of ovulatory activity. Does demonstrated similar metabolic hormones and concentrations of blood metabolites between the two nutritional treatments (100 v. 150% of the nutritional requirements), suggesting a high physiological plasticity between the groups, stabilising their metabolism according to the nutritional history female goats faced, and generating similar reproductive outcomes. The male effect seems to be enough to induce oestrus during the late anoestrous season, irrespective of BCS and BW.
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Hivert, Bénédicte, Claudine Caron, Stéphanie Petit, Cécile Charpy, Corinne Fankam-Siaka, Alain Duhamel, Olivier Tournilhac, Jenny Goudemand, and Pierre Morel. "Clinical and Prognostic Implications of Low or High Level of Von Willebrand Factor (VWF) In Waldenström Macroglobulinemia (WM) Patients (pts). A Clinicopathological Study on 72 Pts." Blood 116, no. 21 (November 19, 2010): 2438. http://dx.doi.org/10.1182/blood.v116.21.2438.2438.
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Abstract Abstract 2438 Introduction: Abnormalities of VWF have been described in WM pts, and several cases of AVWS have been reported. We aimed to describe the frequency of AVWS and the distributions of von Willebrand factor Ristocetin Cofactor activity (VWF:RCo) and antigen (VWF:Ag) levels along with VEGF expression in WM pts. Pts and methods: We systematically assessed both levels of VWF:Rco and VWF:Ag in a series of 72 WM pts (median age: 70 years, 39 to 91 years, sex ratio M/F: 1.6, symptomatic: 55). Diagnostic and treatment criteria for WM fulfilled recommendations of the 2nd international WM workshop. AVWS was suspected when VWF:RCo level was <50% (40% for blood group O pts). Immunostainings for vascular endothelial growth factor (VEGF) and VWF with assessment of microvessel density (MVD) were performed in 23 pts. Results: Mean levels of VWF:Ag and VWF:RCo were 167% and 152% respectively, with a significant negative relationship between both VWF:RCo and VWF:Ag and serum M-component concentration in WM pts with VWF:Ag <130% (p<1×10−4 and p=0.006, respectively). AVWS was suspected in 10 pts with symptomatic WM (median level of VWF:RCo: 31%, Haemorrhage in 4 pts). Pts with suspected AVWS had higher serum monoclonal IgM (mIgM) concentration than remaining pts (p=0.001). Reduction of IgM with plasmapheresis (4 pts) or treatment of WM was associated with an increase in VWF:Ag and VWF:RCo levels. High level of propeptide and increase in the ratio propeptide/VWF suggested an increase in the clearance of mature VWF. However, IgM inhibitory activity was absent in all evaluated pts with suspected AVWS (n=6). VWF immunostaining on bone marrow trephine biopsy did not support an adsorption of VWF on tumoral cells. Pspline proportional hazard regression models including VWF:Ag (p=10−4) and recursive partitioning analyses of survival showed an increase in the hazard for death with the increase in the level of VWF:Ag. Thus, 43 pts (59%) presented with VWF:Ag > 110%, and among these, 13 pts with VWF:Ag > 250%. They had higher level of propeptide (p=0.0006) than pts without abnormality of VWF (VWF:Ag < 110% and no AVWS) but the ratio propeptide/VWF:Ag was not significantly different between both subgroups, suggesting the presence of a chronic endothelial activation. Immunostainings identified a high MVD in 6 of the 23 tested pts, the presence of VEGF on mast cells in 8 pts and on tumoral cells in 13 pts. Pts with high MVD and pts expressing VEGF on mast cells had significantly higher levels of VWF:Ag than other pts (p=0.05 and 0.01 respectively). These pts more frequently had VWF:Ag levels above 250% (2-sided Fisher test: p=0.004 and 0.006 respectively). In addition, pts with high MVD more frequently (p=0.05) expressed VEGF on mast cells than other pts. The 5-year survival of pts with VWF:Ag < 110%, between 110% and 250% and >250% were 96%, 71%, and 44% respectively (p<0.0001, figure A). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (p<0.0001, figure B), independently of international scoring system (p≤0.001), and for survival after sampling (p<0.0001). Conclusion: Taken together, our results support a systematic assessment of VWF:RCo and VWF:Ag in WM pts. Follow-up data supported the importance of the treatment of WM in the management of suspected AVWS. Systematic assessment identified up to 59% of high-risk pts with high level VWF:Ag. The identification of this new prognostic factor raised new issues on the underlying cellular interactions between tumoral cells, mast cells and endothelial cells in WM. Disclosures: No relevant conflicts of interest to declare.
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Adams, Jordan, Aaron B. Norris, Madeline E. Rivera, Luiz Fernando Dias Batista, and Luis O. Tedeschi. "176 The Suitability of Autoclave and Pressure Cooker Washing Methods in Comparison to ANKOM200 to Determine Neutral Detergent Fiber Using Different Feedstuffs and Washing Solutions." Journal of Animal Science 98, Supplement_2 (November 1, 2020): 24. http://dx.doi.org/10.1093/jas/skz397.054.
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Abstract The use of the in vitro gas production (IVGP) technique requires accurate determination of neutral detergent fiber (NDF) residue. However, the NDF determination using standard procedures are not always feasible for IVGP; thus requiring micro-NDF methods, which need autoclave (AC) and pressure cooker (PC) to boil the solution. A complete randomized design using a 3×3 factorial arrangement was implemented to investigate the effect of washing methods (WM: AC, PC, or ANKOM200) and solution ratios (WS: 100 mL neutral detergent solution (ND), 150 mL ND, or 100 mL H2O/g sample) to determine NDF residues, assuming ANKOM200 and 100 mL ND/g as the standard methodology. Each factor combination was performed in triplicate with a replicate being comprised of 12 bottles or bags (two blanks and five feedstuffs in duplicate). Feedstuffs were: alfalfa hay (AH), bermudagrass hay (BH), two high-forage rations (G1 and G2), and a high-concentrate ration (FR). Following each run, bottles were filtered to obtain the NDF. Data were analyzed by diet using a random coefficients model. An interaction of WM ′ WS was present for AH and G1 (P < 0.01), G2 and FR had tendencies (P = 0.08 and 0.06, respectively), whereas BH demonstrated no interaction (P = 0.37). The PC with 100 mL or 150 mL did not differ from the standard methodology for AH, G1, G2, and FR. The BH demonstrated differences between WM and WS (P < 0.01). The PC had lower NDF residue compared to the AC and ANKOM200, whereas H2O had substantially greater NDF residue relative to both ND ratios. We concluded that H2O is not a suitable substitute for ND solution regardless of the feedstuff. Both micro-NDF washing methods may be satisfactory depending on the type of feedstuff used, but further investigation is required.
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Adams, Jordan, Aaron B. Norris, Madeline E. Rivera, Luiz Fernando Dias Batista, and Luis O. Tedeschi. "175 The Suitability of Autoclave and Pressure Cooker Washing Methods in Comparison to ANKOM200 to Determine Neutral Detergent Fiber Using Different Feedstuffs and Washing Solutions." Journal of Animal Science 98, Supplement_2 (November 1, 2020): 79. http://dx.doi.org/10.1093/jas/skz397.186.
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Abstract The use of the in vitro gas production (IVGP) technique requires accurate determination of neutral detergent fiber (NDF) residue. However, the NDF determination using standard procedures are not always feasible for IVGP; thus requiring micro-NDF methods, which need autoclave (AC) and pressure cooker (PC) to boil the solution. A complete randomized design using a 3×3 factorial arrangement was implemented to investigate the effect of washing methods (WM: AC, PC, or ANKOM200) and solution ratios (WS: 100 mL neutral detergent solution (ND), 150 mL ND, or 100 mL H2O/g sample) to determine NDF residues, assuming ANKOM200 and 100 mL ND/g as the standard methodology. Each factor combination was performed in triplicate with a replicate being comprised of 12 bottles or bags (two blanks and five feedstuffs in duplicate). Feedstuffs were: alfalfa hay (AH), bermudagrass hay (BH), two high-forage rations (G1 and G2), and a high-concentrate ration (FR). Following each run, bottles were filtered to obtain the NDF. Data were analyzed by diet using a random coefficients model. An interaction of WM ′ WS was present for AH and G1 (P < 0.01), G2 and FR had tendencies (P = 0.08 and 0.06, respectively), whereas BH demonstrated no interaction (P = 0.37). The PC with 100 mL or 150 mL did not differ from the standard methodology for AH, G1, G2, and FR. The BH demonstrated differences between WM and WS (P < 0.01). The PC had lower NDF residue compared to the AC and ANKOM200, whereas H2O had substantially greater NDF residue relative to both ND ratios. We concluded that H2O is not a suitable substitute for ND solution regardless of the feedstuff. Both micro-NDF washing methods may be satisfactory depending on the type of feedstuff used but further investigation is required.
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Ryu, Ho-sun, Boyoung Jung, Jiyoon Yeo, Jae-Hong Kim, Dongwoo Nam, and In-Hyuk Ha. "Analysis of medical services provided to patients with ankle sprains in Korea between 2015 and 2017: a cross-sectional study of the health insurance review and assessment service national patient sample database." BMJ Open 10, no. 9 (September 2020): e039297. http://dx.doi.org/10.1136/bmjopen-2020-039297.
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ObjectivesTo provide useful information for policy-makers and clinicians by analysing the medical service use—divided into Western medicine (WM) and Korean medicine (KM)—of patients with ankle sprains in South Korea between 2015 and 2017.DesignCross-sectional, retrospective, observational study.SettingTertiary hospitals, WM hospitals, WM clinics, KM hospitals, KM clinics and others in South Korea.ParticipantsWe analysed claim data and patient information from the 2015 to 2017 Health Insurance Review and Assessment National Patient Sample (HIRA-NPS) dataset, including 151 415 patients diagnosed with a ‘dislocation, sprain and strain of joints and ligaments at ankle and foot level’ (10th revision of the International Statistical Classification of Diseases code S93) who used medical services at least once in 3 years between January 2015 and December 2017 in South Korea.Primary and secondary outcome measuresCost of medical care, number of consultations, type of institution visited, types of treatment.ResultsThere were 160 200 consultations and 53 044 patients in 2015, 149 956 consultations and 50 830 patients in 2016 and 140 651 consultations and 47 541 patients in 2017. The total treatment costs were US$3 355 044.21, US$3 245 827.70 and US$3 128 938.46 in 2015, 2016 and 2017, respectively. The most common age was 10–19 years. The most frequent type of visit was KM outpatient visit (56%). Physiotherapy was most common in WM outpatient visits, while acupuncture was most common in KM visits. Most patients used one institution, rather than alternating between WM and KM.ConclusionsBy identifying the trends and costs of treatment methods used for ankle sprains and comparing WM and KM, our data provide basic information for future health policy-making. In addition, the duality of the Korean medical system is highlighted as a possible cause of increased costs.