Auswahl der wissenschaftlichen Literatur zum Thema „WG 168.5“

Background:Objectives:To compare clinical characteristics, pregnancies, and treatments during pregnancies of seronegative and seropositive APS, and analyse factors associated with adverse obstetrical outcomes.Methods:Inclusion criteria were: (1) thrombotic arterial and/or venous; and /or obstetrical primary clinical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies; (3) presence of at least one non-conventional APL among IgA ACL, IgA antiB2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-PE G/M, anti-PS/PT G/M antibodies. The exclusion criteria were: (1) seropositive APS with conventional APS; (2) associated SLE or SLE like (SLE features and / or positive antinuclear autoantibodies); (3) other systemic connective tissue disease (Sjogren’s syndrome, systemic sclerosis, myositis).Results:187 women (mean 33±5 years) with seronegative APS were included from 12 centers in the world and compared to 285 patients with seropositive APS. Seronegative APS have mostly obstetrical phenotypes rather than venous thrombosis in comparison to seropositive APS. The maternal and fetal outcomes and the rates of live births were not significantly different in seronegative and seropositive APS, except for higher rates of intrauterine deaths (15% vs 5%; p=0.03) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) in the seropositive APS group. The cumulative incidence of adverse obstetrical events was significantly improved in treated seronegative APS vs untreated ones (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-LMWH combinationConclusion:Patients with clinical manifestations of APS without conventional APL should undergo testing for non-criteria APL. The diagnosis of seronegative APS could be important for a better care of these patients.Table 1.Characteristics of seronegative and seropositive APS women.Seronegative APSN=187Seropositive APSN=285APS featuresThrombotic APS Arterial APS (n;%)0105 (37)* Venous APS (n;%)9 (6)154 (54)*Obstetrical APS (n;%)168 (89)89 (31)*Mix APS (n;%)8 (4)16 (6)Non criteria features (n;%)16 (9)141 (49)*Obstetrical history Miscarriages (n;%)66 (35)18 (6)* Intrauterine deaths (n;%)60 (32)46 (16)* Prematurity <34 wg (n;%)43 (23)31 (11)*Table 2.Pregnancy outcome and treatment in seronegative and seropositive APS.Seronegative APS pregnanciesN=108Seropositive APS pregnanciesN=75Thrombotic APS Arterial APS (n;%)020 (27)* Venous APS (n;%)8 (7)42 (56)*Obstetrical APS (n;%)93 (86)36 (48)*Mix APS (n;%)6 (6)18 (24)Aspirin (n;%) / Aspirin alone95 (88) / 32 (30)57 (76)* / 2 (3)*LMWH isocoagulant amounts (n;%)63 (58)39 (52)Aspirin-LMWH (n;%)65 (60)55 (73)Preeclampsia/HELLP syndrome (n;%)7 (7)12 (16)*IUGR (n;%)5 (5)7 (10)Fetal loss (n;%)33 (31)22 (29)Miscarriage / Intrauterine deaths23 (21) / 5 (5)11 (15) / 11 (15)*Prematurity<34 weeks of gestation (n;%)6 (6)9 (12)Term of fetal loss (weeks gestation)10±813±7Live births (n;%)75 (69)53 (70)Term of live birth (weeks gestation)38±336±3*Disclosure of Interests: :None declared

Abstract. The work of ISPRS Technical Commission III is devoted to remote sensing. For the XXIVth ISPRS CONGRESS – 2021 Edition (Digital), Technical Commission III received total 201 submissions, including 72 full papers and 138 abstracts. Among these submissions 38 are accepted as peer-reviewed contributions for publication in the ISPRS Annals, 118 were accepted for publication in the ISPRS Archives.These papers are dedicated mostly to topics of the 10 TC III working groups and 4 inter-commission working groups as follows – WG III/1: Thematic Information Extraction; WG III/2: Microwave Remote Sensing; WG III/3: SAR-based Surface Generation and Deformation Monitoring; WG III/4: Hyperspectral Image Processing; WG III/5: Information Extraction from LiDAR Intensity Data; WG III/6: Remote Sensing Data Fusion; WG III/7: Landuse and Landcover Change Detection; WG III/8: Remote Sensing of Atmospheric Environment; WG III/9: Cryosphere and Hydrosphere; WG III/10: Agriculture and Natural Ecosystems Modelling and Monitoring; ICWG III/II: Planetary Remote Sensing and Mapping; ICWG III/Iva: Disaster Assessment, Monitoring and Management; ICWG III/IVb: Remote Sensing Data Quality; ICWG III/IVc: Environment and Health. The papers and abstracts were evaluated by the experts in the field and Working Group Chairs according to content, significance, originality, relevance, and clearness of presentation.We would like to thank the authors for their contributions, the reviewers for their reviewing, the working group officers for their efforts on calling for papers, and the organizers of the Congress for publishing this volume.

Abstract. The work of ISPRS Technical Commission III is devoted to remote sensing. For the XXIVth ISPRS CONGRESS – 2021 Edition (Digital), Technical Commission III received total 201 submissions, including 72 full papers and 138 abstracts. Among these submissions 38 are accepted as peer-reviewed contributions for publication in the ISPRS Annals, 118 were accepted for publication in the ISPRS Archives.These papers are dedicated mostly to topics of the 10 TC III working groups and 4 inter-commission working groups as follows – WG III/1: Thematic Information Extraction; WG III/2: Microwave Remote Sensing; WG III/3: SAR-based Surface Generation and Deformation Monitoring; WG III/4: Hyperspectral Image Processing; WG III/5: Information Extraction from LiDAR Intensity Data; WG III/6: Remote Sensing Data Fusion; WG III/7: Landuse and Landcover Change Detection; WG III/8: Remote Sensing of Atmospheric Environment; WG III/9: Cryosphere and Hydrosphere; WG III/10: Agriculture and Natural Ecosystems Modelling and Monitoring; ICWG III/II: Planetary Remote Sensing and Mapping; ICWG III/Iva: Disaster Assessment, Monitoring and Management; ICWG III/IVb: Remote Sensing Data Quality; ICWG III/IVc: Environment and Health. The papers and abstracts were evaluated by the experts in the field and Working Group Chairs according to content, significance, originality, relevance, and clearness of presentation.We would like to thank the authors for their contributions, the reviewers for their reviewing, the working group officers for their efforts on calling for papers, and the organizers of the Congress for publishing this volume.

Somatostatin (SRIF), by acting mainly through sst2 and sst5 receptors, is a potent inhibitor of hormonal secretion by the human anterior pituitary gland. However, the pattern of protein expression of these SRIF receptors remains unknown during pituitary development. To get further insights into the physiological role of SRIF receptors in human development and pituitary function, the present study examined the developmental expression of the sst2 and sst5 receptors in the individual cell types of the anterior human pituitary. Thirteen fetal human pituitaries were investigated between 13 to 38 weeks of gestation (WG) by double-labeling immunofluorescence with antibodies raised against sst2 or sst5 receptors and GH, LH, FSH, TSH, or pro-opiomelanocortin proteins. SRIF immunoreactivity in the hypothalamus and median eminence was investigated at the same developmental ages. Immunoreactivity for the sst2 receptor was evident as early as 13 to 15 WG and onward mainly in TSH-, LH-, and FSH-expressing cells, whereas sst5 immunoreactivity was apparent at the late development stages (35–38 WG). GH-expressing cells mainly expressed sst5 immunoreactivity. SRIF-positive fibers and cells were detected as soon as 13 to 16 WG in the hypothalamus and median eminence and their densities increased with gestational age. The early appearance of hypothalamic SRIF cells and fibers suggests a physiological link between SRIF and its receptors during pituitary development. Whereas sst2 receptors might play a primary role in the differentiation and regulation of TSH, LH, and FSH cells, sst5 receptors appear to be mainly involved in GH regulation from birth onward.

The present study aims to identify combinations of active substances for the complex control of pathogens and pests on eggplant crops in the field. The experiments were conducted between 2016 - 2017, in field conditions, using the variety of eggplant Luiza and the following experimental variants: V 1 - Acrobat MZ 69 WG 0.2% + Mospilan 20 SG 0.04%; V 2 - Acrobat MZ 69 WG 0.2% + Vertimec 1.8 EC 0.1%; V 3 - Acrobat MZ 69 WG 0.2% + Laser 240 SC 0.05%; V 4 - Melody Compact 49 WG 0.2% + Mospilan 20 SG 0.04%; V 5 - Melody Compact 49 WG 0.2% + Vertimec 1.8 EC 0.1%; V 6 - Melody Compact 49 WG 0.2% + Laser 240 SC 0.05%; V 7 - Ortiva Top 0.1% + Mospilan 20 SG 0.04%; V 8 - Ortiva Top 0.1% + Vertimec 1.8 EC 0.1%; V 9 - Ortiva Top 0.1% + Laser 240 SC 0.05%; V 10 - untreated control. The average efficacy of the treatment variants experienced in 2016 and 2017 varied between 83.2% (V4) and 85.0% (V8) depending on the combinations of products pathogens and pests control. Analyzing the yields obtained (34.6 -44.0 t / ha in 2016 and 33.5 - 43.1 t / ha in 2017), compared to the untreated control variant (30.4 t / ha in 2016 and 31.1 t / ha in 2017), it is found that the yield differences obtained in addition to the untreated control variants were in all cases, very significant.

5′-AMP-activated protein kinase (AMPK) signaling initiates adaptive changes in skeletal muscle fibers that restore homeostatic energy balance. The purpose of this investigation was to examine, in rats, the fiber-type protein expression patterns of the α-catalytic subunit isoforms in various skeletal muscles, and changes in their respective contents within the tibialis anterior (TA) after chronic low-frequency electrical stimulation (CLFS; 10 Hz, 10 h daily), applied for 4 ± 1.2 or 25 ± 4.8 days. Immunocytochemical staining of soleus (SOL) and medial gastrocnemius (MG) showed that 86 ± 4.1 to 97 ± 1.4% of type IIA fibers stained for both the α1- and α2-isoforms progressively decreased to 63 ± 12.2% of type IID/X and 9 ± 2.4% of IIB fibers. 39 ± 11.4% of IID/X and 83 ± 7.9% of IIB fibers expressed only the α2 isoform in the MG, much of which was localized within nuclei. α1 and α2 contents, assessed by immunoblot, were lowest in the white gastrocnemius [WG; 80% myosin heavy chain (MHC) IIb; 20% MHCIId/x]. Compared with the WG, α1 content was 1.6 ± 0.08 ( P < 0.001) and 1.8 ± 0.04 ( P < 0.0001)-fold greater in the red gastrocnemius (RG: 13%, MHCIIa) and SOL (21%, MHCIIa), respectively, and increased in proportion to MHCIIa content. Similarly, α2 content was 1.4 ± 0.10 ( P < 0.02) and 1.5 ± 0.07 ( P < 0.001)-fold greater in RG and SOL compared with WG. CLFS induced 1.43 ± 0.13 ( P < 0.007) and 1.33 ± 0.08 ( P < 0.009)-fold increases in the α1 and α2 contents of the TA and coincided with the transition of faster type IIB and IID/X fibers toward IIA fibers. These findings indicate that fiber types differ with regard to their capacity for AMPK signaling and that this potential is increased by CLFS.

We report the first observation of an Fe3+ maser oscillation at zero magnetic field inside a whispering gallery (WG) sapphire resonator. The described maser is new in that it operates at zero-field and with low ion concentration. At zero-field, the Fe3+ ion shows a 3-level structure related to the electron spin resonance (ESR). By applying a 31 GHz pump (|1/2〉 → |5/2〉), the ion operates as a maser at 12 GHz (|5/2〉 → |3/2〉). The maser effect is made possible by the high Q-factor (several 108) of the cryogenic whispering gallery resonator. Additionnaly, the sharp cavity resonance provides short term stability. Preliminary measurements indicate a frequency stability of parts in 10-14 (Allan deviation at 100 s), still limited by the instrument. The ultimate maser stability is still unknown.

Abstract Survival, proliferation, and resistance to chemotherapy in CLL cells have been consistently shown to be associated with the activity of the B-cell receptor (BCR) and the associated downstream pathways activated by it. Key molecules in this pathway are Lyn and Syk (Spleen tyrosine kinase), as well as PI3K, Btk (Bruton’s tyrosine kinase), and ERK. Dasatinib, given at standard doses, allows for serum levels well above 11 nM, the IC50 for the direct suppression of Lyn kinase and Btk. We have previously shown that dasatinib used as a single agent in patients with relapsed CLL results in lymph node responses in 60% of patients and partial responses in 20% of patients as defined by NCI-WG criteria. In the current study, patients with relapsed CLL were treated with a regimen combining dasatinib at 140 mg/day, days 1-14, with fludarabine (F) 25 mg/m2/day, days 1-3, and rituximab (R) 375 mg/m2 per cycle, repeated every 28 days, for up to 6 cycles. Patients were followed closely for response with CT scans every 2 months initially. Among the first 10 patients treated, the schedule of treatment was altered to determine signal transduction effects and resultant apoptosis of the CLL cells due to the different components of the regimen. Hence, only dasatinib was given on Day 1, only fludarabine and rituximab on Day 3, and all 3 drugs on Day 4. Blood samples were obtained from the patients before dosing and at 6 hours after treatment to measure effects on the CLL cells, which were isolated by standard Ficoll separation and frozen until the assays could be performed. For these 10 patients the median time to progression (TTP) was 21 months, and the initial clinical response was as follows: Site CR CRi PR SD PD ORR 95% CI Blood 4 2 4 0 0 100% 74%, 100% Nodes 6 1 1 1 1 80% 49%, 96% CT 2 0 2 6 0 40% 15%, 70% IWCLL 2 0 2 5 1 40% 15%, 70% Key: CR=complete response in blood = < 4,000/ul lymphocytes, CR in nodes = no nodes palpable by PE, CRi = complete response with incomplete blood recovery, PR=partial response, SD=stable disease, PD=progressive disease, ORR=overall response rate, CI=confidence interval. IWCLL = International Workshop on CLL criteria. The patterns of signal transduction in response to the various drugs at 6 hours are shown in aggregate for the patients below. The numbers represent the ratio of phosphorylated protein to total protein at the times indicated with respect to their baseline levels set as 100%. The phosphorylation sites tested were p-Lyn (Y416), p-Syk (Y352), p-ERK1/2 (T202/Y204). Phosphorylation at 6 h after indicated treatment – % of baseline ± SE (N=7): Day 1 (D) Day 3 (F+R, no D) Day 4 (D+F+R) p-Lyn/Lyn: 42% ± 3% 207% ± 63% 58% ± 13% p-Syk/Syk: 34% ± 15% 122% ± 67% 36% ± 15% p-ERK/ERK : 64% ± 22% 168% ± 40% 56% ± 22% The patterns of signal transduction for the 3 patients with the most favorable outcome (TTP and OS) were compared to that for the 4 patients with the poorest clinical outcome. The baseline ratios of phospho-ERK1/2 to ERK1/2 (pre-treatment) correlated most strongly with outcome. Those with a good outcome exhibited low basal p-ERK/ERK (mean 1.0, range 0.1 to 1.8 percent), while patients with a poor outcome exhibited high basal p-ERK/ERK (mean 22.1, range 2.2 to 65.6 percent). Conclusions: For most patients, dasatinib inhibits (directly or indirectly) phosphorylation of Lyn kinase, Syk kinase, and ERK1/2 in the first 6 hours. The degree of apoptosis (to be presented, but not shown here) resulting from this is variable and is probably affected by activation of the PI3K/Akt pathway and other pathways. The long-term clinical outcome of our patients correlated strongly with the baseline phosphorylation of ERK1/2, suggesting that future treatments of patients with CLL might benefit from targeting ERK directly, or by targeting other molecules in the MAPK pathway. Disclosures Off Label Use: Dasatinib for treatment of CLL is off-label use. We present a rationale for its use in CLL patients.. Brown:Sanofi, Onyx, Vertex, Novartis, Boehringer, GSK, Roche/Genentech, Emergent, Morphosys, Celgene, Janssen, Pharmacyclics, Gilead: Consultancy. Attar:Agios: Employment. Fathi:Seattle Genetics, Inc.: Consultancy, Research Funding; Takeda pharmaceuticals International Co.: Research Funding; Exelixis: Research Funding; Ariad: Consultancy.

The purpose of the present study was to determine whether hindlimb unloading of rats alters vasoconstrictor and myogenic responsiveness of skeletal muscle arterioles. After either 2 wk of hindlimb unloading (HU) or cage control (C), second-order arterioles were isolated from the white portion of gastrocnemius (WG; C: n = 9, HU: n = 10) or soleus (Sol; C: n = 9, HU: n = 10) muscles and cannulated with two micropipettes connected to reservoir systems for in vitro study. Intraluminal pressure was set at 60 cmH2O. The arterioles were exposed to step changes in intraluminal pressure ranging from 20 to 140 cmH2O to determine myogenic responsiveness and to KCl (10–100 mM) and norepinephrine (10−9–10−4M) to determine vasoconstrictor responsiveness. Although maximal diameter of WG arterioles was not different between C (185 ± 12 μm) and HU (191 ± 14 μm) rats, WG arterioles from HU rats developed less spontaneous tone (C: 33 ± 5%, HU 20 ±3%), were unable to maintain myogenic tone at pressures from 140 to 100 cmH2O, and were less sensitive to the vasoconstrictor effects of KCl and norepinephrine (as indicated by a higher agonist concentration that produced 50% of maximal vasoconstrictor response). In contrast, maximal diameter of Sol arterioles from HU rats (117 ± 12 μm) was smaller than that in C rats (148 ± 14 μm). However, the development of spontaneous tone (C: 30 ± 4%, HU: 36 ± 5%), myogenic activity, and the responsiveness to vasoconstrictor agonists were not different between Sol arterioles from C and HU rats. These results indicate that hindlimb unloading diminishes the myogenic autoregulatory and contractile responsiveness of arterioles from muscle composed of type IIB fibers and suggest that the compromised ability to elevate vascular resistance after exposure to microgravity may be related to these vascular alterations. In addition, hindlimb unloading appears to induce vascular remodeling of arterioles from muscle composed of type I fibers, as indicated by the decrease in maximal diameter of arterioles from Sol muscle.

Abstract Abstract 3902 Chemoimmunotherapy (CIT) is highly effective treatment and standard of care for patients (pts) with CLL. Response to treatment by NCI-WG/IWCLL criteria correlates with outcome; pts who achieve complete remission (CR) have superior progression-free and overall survival compared to pts who achieve partial remission (PR); and pts who fail therapy have the poorest outcome. Emerging data indicate improved outcomes for pts who achieve minimal residual disease (MRD)-free status in blood or bone marrow (BM) by end of treatment. We are conducting a clinical trial to prospectively evaluate pretreatment pt characteristics and prognostic factors and correlations with NCI-WG response, MRD-free status, and time to event outcomes with standard frontline fludarabine, cyclophosphamide, and rituximab (FCR) CIT. A total of 197 pts have been registered, 160 have completed treatment and are evaluable for response by NCI-WG criteria, and 127 have BM MRD status evaluated by standard 4-color flow cytometry at Course 3 and/or end of treatment. We report on pretreatment characteristics associated with MRD-free status at end of treatment. For the 160 pts evaluable for response by NCI-WG criteria, 63% were male; the median (range) age, β2M, and absolute lymphocyte count (ALC) were 58 yrs (38–84), 3.6 mg/l (1.3–14.1), and 78.7 K/μl (.8–394), respectively. The percent pts with Rai high-risk disease, unmutated IGHV status, ZAP70+ by immunohistochemistry (IHC) and CD38+ (30% cutoff) was 35%, 60%, 63%, and 37%, respectively. According to the hierarchical categorization, FISH demonstrated 17p del in 9%, 11q del in 18%, +12 in 17%, 13q del in 36%, and no abnormality in 20% of pts. The median number of FCR courses given was 6; 57% received all intended 6, 21% received 4–5, and 23% received ≤3. Of the 160 pts, 63% achieved CR, 12% nodular PR (nPR), 23% PR and 3% did not respond. Of 127 pts with BM evaluated by 4-color flow cytometry at end of treatment, 56% were MRD-free. Of 71 MRD-free pts, 27 were negative at end of course 3, 33 converted to negative after course 3, and 11 were negative at end of treatment but did not have a course 3 evaluation. Univariable Chi-square analyses demonstrated pretreatment β2M, IGHV mutation status, 17p del, and +12 correlated with MRD-free status at end of treatment (Table). The following did not correlate: age, Rai stage, WBC, ALC, HGB, PLT, ZAP70, CD38, or number of FCR courses received. Multivariable logistic regression model identified β2M≥4 mg/l (odds ratio=.78; p=.007) and unmutated IGHV (odds ratio=.77; p=.006) as independently associated with lower likelihood to achieve MRD-free status. In conclusion, mutated IGHV and β2M <4 mg/l are independently associated with increased likelihood of achieving MRD-free status with frontline FCR CIT; further follow up is needed to correlate MRD-free status with improved survival outcomes for patients treated on this trial.TableNCI-WG Responsen% MRD-NegativeCR8071nPR150PR3047*NR20Pretreatment Characteristicn% MRD-Negativep-valueAge (yrs) <65100600.07≥652741Rai Stage Low & Int-risk82610.12High-risk4347b2M (mg/l) <473640.02≥44942ALC (K/ml) <5040560.86≥508755IGHV Mutated47700.006Unmutated6244ZAP70 IHC Negative41610.28Positive7351CD38+ ≤7%4863Ref**8–29%27480.23≥30%42550.46FISH 13q del4556RefNone22680.32+1220800.0611q del20400.2417p del10200.04*All MRD-free are PR due to cytopenia, with no evidence of CLL**Used as reference or comparison group Disclosures: No relevant conflicts of interest to declare.